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1.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 385-388, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374258

RESUMO

Objective: To investigate the role of cell autophagy in lung ischemia/reperfusion injury in rats. Methods: Forty SD rats were randomly divided into 5 groups (n=8): ①Sham operated group (sham group):just open rat chest for 3.5 h; ②Ischemia/reperfusion group (I/R group):after open chest, clamp pulmonary hilus for 0.5h then reperfusion for 3 h; ③Solvent group (DMSO group): intraperitoneal injection of DMSO solution for 1h before operation; ④Autophagic inhibitor group (3-MA group); ⑤Autophagic agonist group (Rap group): intraperitoneal injection of autophagic agonist rapamycin before operation; the rest operations of DMSO, 3-MA and Rap groups are the same as that of I/R group. At the end of the experiment, the rats were killed by euthanasia-killing. The lung tissues were collected and the wet/dry weight ratio (W/D) and total lung water content (TLW) of the lung tissues were detected. The lung tissue structure and cell ultramicro morphology were observed by light microscopy and electron microscopy and the injuried alveolar rate(IAR) was calculated. The autophagy-related protein expressions were detected by Western blot. Results: Compared with sham group, the levels of W/D, TLW and IAR were increased, the expressions of autophagy related protein and p-AMPK, Beclin 1, LC3 II were also increased in other four groups, while the protein expressions of p-mTOR and p62 were decreased significantly (P< 0.05 or P<0.01). Under the light microscope, the other groups of lung tissue had edema and exudation in varying degrees, the structure of alveoli was disordered, the ultrastructural damage of cells was aggravated under the electron microscope, and autophagosome could be observed. Compared with DMSO group, the expressions of autophagy related protein, the levels of W/D, TLW and IAR in 3-MA group were decreased (P<0.05 or P<0.01), the edema of lung interstitial was lighter, and less cells were found in alveolar cavity. Ultrastructural damage was also lighter and with less autophagosome. Besides, there was no significant difference among I/R, DMSO and Rap groups (P>0.05). Conclusion: Autophagy can be activated during ischemia/reperfusion in rats to induce lung injury.


Assuntos
Lesão Pulmonar , Traumatismo por Reperfusão , Animais , Autofagia , Isquemia , Pulmão , Ratos , Ratos Sprague-Dawley
2.
Sheng Li Xue Bao ; 71(2): 301-310, 2019 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-31008490

RESUMO

The aim of this study was to investigate the regulatory role of retinoid X receptor (RXR)-mediated oxidative stress pathway in rat pulmonary ischemia/reperfusion injury (PIRI) and the underlying mechanism. Seventy-seven male Sprague-Dawley (SD) rats were randomly divided into 7 groups (n = 11): control group, sham group, sham+9-cis-retinoid acid (9-cRA, RXR agonist) group, sham+HX531 (RXR inhibitor) group, ischemia/reperfusion (I/R) group, I/R+9-cRA group, and I/R+HX531 group. The unilateral lung I/R model was established by obstruction of left lung hilus for 30 min and reperfusion for 180 min in vivo. The rats in I/R+9-cRA and I/R+HX531 groups were given intraperitoneal injection of 9-cRA and HX531 before thoracotomy. After reperfusion, the left lung tissue was taken to evaluate the lung tissue injury, and the oxidative stress-related indexes of the lung tissue were detected by the corresponding kits. The lung tissue morphology and the ultrastructure of the alveolar epithelial cells were observed by HE staining and transmission electron microscope, respectively. The protein expression of RXR in lung tissue was observed by immunofluorescence labeling method, and the expression level of nuclear factor E2-related factor (Nrf2) protein was detected by Western blot. The results showed that, compared with the sham group, the I/R group exhibited obviously injured lung tissue, decreased SOD activity, increased MDA content and MPO activity, and down-regulated expression level of Nrf2 protein. Compared with the I/R group, the I/R+9-cRA group showed alleviated lung tissue injury, increased activity of SOD, decreased MDA content and MPO activity, and up-regulated expression levels of RXR and Nrf2 protein. The above-mentioned improvement effects of 9-cRA were reversed by HX531 treatment. These results suggest that RXR activation can effectively protect the lung tissue against I/R injury, and the mechanism may involve the activation of Nrf2 signaling pathway, the enhancement of antioxidant level and the reduction of oxidative stress response.


Assuntos
Pulmão/fisiopatologia , Estresse Oxidativo , Traumatismo por Reperfusão , Receptores X de Retinoides/fisiologia , Animais , Masculino , Fator 2 Relacionado a NF-E2/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
3.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(1): 8-13, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926651

RESUMO

OBJECTIVE: To investigate the effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion (I/R) induced myocardial injury in mice. METHODS: Forty healthy SPF male C57BL/6J mice were divided into 4 groups randomly (n=10):sham operation group (Sham group), lung I/R group (I/R group), endoplasmic reticulum stress (ERS) pathway agonist Tunicamycin group (TM) and ERS inhibitor 4-phenyl butyric acid group (4-PBA). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion. In sham group, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min. In TM and 4-PBA groups, TM 1mg/kg and 4-PBA 400 mg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model. At 180 min of reperfusion, blood samples were collected from the orbit for determination of myocardial enzyme. The animals were then sacrificed, and hearts were removed for determination of light microscope, TUNEL, Caspase 3 enzymatic activity, real-time polymerase chain reaction and Western blot. RESULTS: Compared with sham group, the cardiomyocytes had obvious damage under light microscope, and the serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-Jun N-terminalkinase(p-JNK), Caspase 12, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulated protein 78(GRP78) protein and mRNA were up-regulated in I/R, TM and 4-PBA groups (P<0.01). Compared with I/R group, the cardiomyocytes damage was obvious under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-JNK, Caspase 12, CHOP and GRP78 protein and mRNA were up-regulated in group TM; while all above changes were relieved in group 4-PBA (P<0.01). Compared with TM group, the cardiomyocytes damage was relieved under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were decreased significantly, the expressions of p-JNK, Caspase 12,CHOP and GRP78 protein and mRNA were down-regulated in group 4-PBA. CONCLUSIONS: The excessive endoplasmic reticulum stress participates in myocardial injury induced by lung ischemia/reperfusion (I/R) and inhibit excessive endoplasmic reticulum stress response can relieved myocardial injury.


Assuntos
Estresse do Retículo Endoplasmático , Traumatismos Cardíacos/fisiopatologia , Pulmão/patologia , Traumatismo por Reperfusão , Animais , Apoptose , Caspase 12 , Caspase 3/metabolismo , Creatina Quinase Forma MB/sangue , Proteínas de Choque Térmico/metabolismo , L-Lactato Desidrogenase/sangue , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Distribuição Aleatória , Fator de Transcrição CHOP/metabolismo
4.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(2): 137-142, 2018 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926678

RESUMO

OBJECTIVES: To investigate the effects of dexmedetomidine (Dex) on injury of A549 cells induced by hypoxia/reoxygenation(H/R)and the influence of C/EBP homologous protein (CHOP) expression. METHODS: Logarithmic growth phase A549 cells(it originated from alveolar type Ⅱ epithelial cell line) were randomly divided into 4 groups (n=10):normoxic control group (N), Dex group (D), hypoxia/reoxygenation group (H), hypoxia/reoxygenation + Dex group(HD). At the beginning of modeling, 1 nmol/L Dex was puted into D and HD groups. N and D groups were cultured in the normoxic incubator for 30 h. H and HD group were incubated in the anoxic cultivation for 6 h, fo llowed by normoxic culture for 24 h. Then A549 cells were observed under the inverted microscope to observe the morphological changes. Cell activity was detected by cell counting Kit-8(CCK-8) and the apoptosis index(AI) was detected by in situ end labeling (TUNEL) method. The expression of CHOP、glucose-regulated protein of molecular weight 78 kDa (Grp78)、cysteinyl aspirate-specificprotease-3 (caspase-3) protein and CHOP、Grp78 mRNA were detected by Western blot and RT-PCR. RESULTS: Compared with N group, the number of adherent cells in H group decreased significantly, and cell morphology changed. The absorbance value in H group decreased obviously (P<0. 01). The AI value and expression of CHOP, Grp78, caspase-3 proteins and CHOP, Grp78 mRNA were significantly increased (P<0.01). Compared with H group, the cell damage in HD group was decreased, the absorbance value increased (P<0.01), the number of apoptosis cells decreased relatively (P<0.01), the expression of CHOP, caspase-3 protein and CHOP mRNA decreased (P<0. 01). CONCLUSIONS: Dex has notable effects against H/R injury, which may be related to effective inhibition of apoptosis mediated by the CHOP's signal path.


Assuntos
Apoptose , Dexmedetomidina/farmacologia , Fator de Transcrição CHOP/fisiologia , Células A549 , Hipóxia Celular , Humanos
5.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(5): 408-413, 2018 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-30788919

RESUMO

OBJECTIVE: To investigate the effect of Yiqi Wenyang Huoxue Huatan Fang (YWHHF) on alleviating hypoxia-hypercarbia pulmonary hypertension by inhibiting endothelial-mesenchymal transition (EndoMT) via BMP-7/Smads pathway. METHODS: Fifty male healthy SD rats of clean grede, weighting (180~220) g, were randomly divided into 5 groups (n=10):normoxia group (N), hypoxia-hypercarbia group (HH); YWHHF high dose group (YH), middle dose group (YM) and low dose group (YL). The rats in N group were kept in normal oxygen environment, the remaining four groups were intermittently exposed to hypoxia-hypercarbia environment (9%~11% O2, 5%~6% CO2) for 4 weeks, 6 days a week, 8 hours per day. The rats in YH, YM, YL groups were received YWHHF gavage in a dosageof 0.6, 0.3, 0.15g/kg respectively (3 ml/kg),the rats in N and HH groups were received equal volume of normal saline. After 4 weeks, the mean pulmonary arterial pressure(mPAP) was detected,the right ventricular free wall and left ventricle plus ventricular septum were isolated to determine the right ventricular hypertrophy index. Lung ultrastructural changes were surveyed under an electronic microscopy, the changes of pulmonary artery structure surveyed by immunofluorescence, the mRNA levels of alpha-smooth muscle actin (α-SMA)、platelet endothelial cell adhesion molecule-1 (CD31)、bone morphogenetic protein-7 (BMP-7)、drosophila mothers against decapentaplegic protein1/5/8 (Smad1/5/8) were detected by RT-PCR, and the protein levels of α-SMA、CD31、BMP-7、p-Smad1/5/8 and Smad1/5/8 were detected by Western blot. RESULTS: Compared with N group, mPAP and the right ventricular hypertrophy index were increased,some significant injuries also were discovered under microscopic observation,the mRNA and protein expression of α-SMA was increased, and the mRNA expressions of CD31、BMP-7、Smad1/5/8 were decreased in the other four groups, the protein expressions of CD31、BMP-7、p-Smad1/5/8 were decreased(P<0.05). Compared with HH group, the above changes in YH、YM、YL groups were all improved (P<0.05). CONCLUSIONS: YWHHF can inhibit EndoMT to alleviate pulmonary hypertension, and the mechanism may be related to the promotion of the expression of BMP-7/Smads pathway.


Assuntos
Hipertensão Pulmonar , Animais , Hipercapnia , Hipertensão Pulmonar/induzido quimicamente , Hipóxia , Masculino , Artéria Pulmonar , Ratos , Ratos Sprague-Dawley
6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(4): 327-333, 2018 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-30788940

RESUMO

OBJECTIVE: To observe the pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia, and to explore the role of endoplasmic reticulum stress in pulmonary hypertension. METHODS: Forty SD rats were random-ly divided into four groups:normoxic control group (N), hypoxia hypercapnia group (HH), ERS inhibitor 4-phenylbutyric acid group (4-PBA), endoplasmic reticulum stress (ERS) pathway agonist tunicamycin group (TM), ten rats in each group.The mean pulmona-ry artery pressure (mPAP), mean carotid artery pressure (mCAP) and right ventricular hypertrophy index of rats in each group were measured.Pulmonary artery smooth muscle cells were identified by immunofluorescence α-smooth muscle actin (α-SMA).Morphologi-cal changes of lung tissue and pulmonary artery were observed by electron microscope.The apoptotic index of pulmonary artery smooth muscle cells in each group was detected by TUNEL.Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), c-Jun N-terminal kinase (JNK) and cysteinyl aspartate specific proteinase-12 (caspase-12) mRNA and protein in each group. RESULTS: ①Compared with the N group, the mPAP, the ratio of right ventricle weight to left ventricle plus ventricular septum weight[RV/(LV+S)]and the ratio of pulmonary artery wall area to total tube area (WA/TA) were increased (P<0.01), and the ratio of pulmonary artery luminal area to total tube area (LA/TA) were decreased (P<0.01), pulmonary artery smooth muscle cell apoptosis index were decreased (P<0.05 or P<0.01) in HH group, 4-PBA group and TM group.ERS related protein and mRNA expressions were increased, the differences were statistically significant.②Compared with the HH group, the mPAP, [RV/(LV+S)]and WA/TA of 4-PBA group were decreased (P <0.01), LA/TA and pulmonary artery smooth muscle cell apoptosis index were increased (P<0.01, P<0.05).The expressions of ERS related protein and mRNA were all decreased (P<0.05 or P<0.01).③Compared with the HH group, the mPAP, [RV/(LV+S)]and WA/TA of TM group were increased (P<0.05 or P<0.01), pulmonary artery middle layer thickened, LA/TA and pulmonary artery smooth muscle cell apoptotic index were decreased (P<0.01).ERS related protein and mRNA expressions were increased with statistical significance except GRP78 protein. CONCLUSIONS: Pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia may be related to the excessive proliferation of pulmonary artery smooth muscle cells and too little apopto-sis;ERS related factors (JNK, caspase-12 and CHOP) are involved in the regulation of pulmonary hypertension induced by hypoxia hypercapnia.


Assuntos
Hipercapnia , Hipertensão Pulmonar , Animais , Estresse do Retículo Endoplasmático , Hipóxia , Artéria Pulmonar , Ratos , Ratos Sprague-Dawley
7.
Sheng Li Xue Bao ; 69(4): 413-421, 2017 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-28825099

RESUMO

The purpose of the present study was to investigate the effect of excessive endoplasmic reticulum stress (ERS) on the brain damage in hypoxia hypercapnia induced pulmonary hypertension (HHPH) rats. Forty healthy SPF male SD rats were randomly divided into four groups (n = 10 for each): control group, hypoxia hypercapnia group, ERS pathway agonist tunicamycin (TM) group and ERS pathway inhibitor 4-phenylbutyric acid (4-PBA) group. The rats of control group lived in normal environment, while the rats of other three groups were raised for four weeks in the tank with 8.5%-11% O2 and 5%-6% CO2. TM (0.08 mg/kg, twice a week) and 4-PBA (80 mg/kg, daily) were respectively intraperitoneally injected into the rats of TM and 4-PBA groups, and the hypoxia hypercapnia group was given the same volume of normal saline. The mean pulmonary artery pressure and heart perfusion of the rats were determined and recorded after four-week raising. Then the brain tissue of the rats were quickly taken out for the brain water content measuring and morphological changes observing. The Caspase-3 activity and the apoptotic index of the brain cells were also determined. The protein and mRNA expressions of p-JNK, Caspase-12, CHOP and GRP78 in brain tissues were detected by Western blot and RT-PCR. The results showed that compared with the control group, the mean pulmonary artery pressure, brain water content and brain cells apoptotic index, Caspase-3 activity, the protein and mRNA levels of p-JNK, Caspase-12, CHOP and GRP78 were increased (P < 0.05), and the brain tissues of the rats were obviously damaged in the rats raised in the hypoxia hypercapnia environment; compared with hypoxia hypercapnia group, the mean pulmonary artery pressure, brain water content, brain apoptotic index and Caspase-3 activity, p-JNK, Caspase-12, CHOP, GRP78 protein and mRNA expressions in TM group were increased (P < 0.05), and the brain tissues of the rats were obviously damaged, while all above changes were relieved in 4-PBA group (P < 0.05). These results suggest that excessive ERS may participate in the brain injury induced by HHPH in rats and inhibition of excessive ERS can relieve the brain injury in the rats with HHPH.


Assuntos
Lesões Encefálicas/patologia , Estresse do Retículo Endoplasmático , Hipercapnia/patologia , Hipertensão Pulmonar/fisiopatologia , Hipóxia/patologia , Animais , Apoptose , Encéfalo , Caspase 12/metabolismo , Caspase 3/metabolismo , Proteínas de Choque Térmico/metabolismo , MAP Quinase Quinase 4/metabolismo , Masculino , Fenilbutiratos/farmacologia , Ratos , Ratos Sprague-Dawley , Fator de Transcrição CHOP/metabolismo , Tunicamicina/farmacologia
8.
Sheng Li Xue Bao ; 69(4): 437-444, 2017 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-28825102

RESUMO

To investigate the effects of dexmedetomidine (DEX) on hypoxia/reoxygenation (H/R) injury-induced cell apoptosis and caspase-12 expression, A549 cells were randomly divided into 4 groups: control group, DEX group, H/R group and DEX+H/R group. Cells of control and DEX groups were cultured in the normoxic incubator for 30 h. Cells of H/R and DEX+ H/R groups were incubated in the anoxic cultivation for 6 h, followed by normoxic culture for 24 h, and DEX (1 nmol/L) was added into the culture medium in DEX and DEX+H/R groups. Morphological changes were observed under the inverted microscope. Cell viability was detected by CCK-8. The apoptosis index (AI) of A549 cells was detected by TUNEL method. The activity of caspase-3 enzyme in cells was detected by using caspase-3 kit. The expressions of GRP78, caspase-12 protein and mRNA were determined by Western blot and RT-PCR respectively. Compared with control group, the morphological changes of the cultured cells were observed: some of the cell fusion occurred and the shape of the cells was multilateral; the cell viability was decreased significantly (P < 0.01), the number of apoptotic cells and the AI value, caspase-3 activity, and the expressions of GRP78, caspase-12 protein/mRNA were significantly increased (P < 0.01) in H/R group. While the administration of DEX alleviated the H/R injury-induced cell damage, obviously increased the cell viability (P < 0.01), significantly decreased the increment of apoptotic cells and the AI value induced by H/R injury (P < 0.01), and also dramatically decreased the H/R injury-induced high level of caspase-3 activity (P < 0.01) as well as high expression of caspase-12 protein and mRNA (P < 0.01). Taken together, the results suggest that DEX can effectively protect A549 cells from the H/R injury, which may be mediated by down-regulating the expression of caspase-12 and inhibiting cell apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 12/metabolismo , Dexmedetomidina/farmacologia , Células A549 , Caspase 3/metabolismo , Hipóxia Celular , Linhagem Celular , Sobrevivência Celular , Citoproteção , Proteínas de Choque Térmico/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Substâncias Protetoras/farmacologia
9.
Sheng Li Xue Bao ; 69(1): 47-54, 2017 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-28217807

RESUMO

The present study was to investigate the role of TRPC6 in pulmonary artery smooth muscle cells (PASMCs) proliferation and apoptosis under hypoxia and hypercapnia. PASMCs were isolated from chloral hydrate-anesthetized male Sprague-Dawley (SD) rats. Cellular purity was assessed by immunofluorescence staining for smooth muscle α-actin under fluorescence microscopy. Passage 4-6 PASMCs were starved for 24 h in serum-free DMEM and divided into 5 groups randomly: normoxia, hypoxia and hypercapnia, DMSO, TRPC6 inhibitor SKF-96365 and TRPC6 activator OAG groups. The normoxic group was incubated under normoxia (5% CO2, 21% O2, 37 °C) for 24 h, and the others were incubated with corresponding drugs under hypoxic and hypercapnic (6% CO2, 5% O2, 37 °C) atmosphere for 24 h. TRPC6 mRNA was detected by reverse transcription-PCR. TRPC6 protein was detected by Western blotting. The proliferation of PASMCs was performed by CCK-8 kit. Apoptosis of the PASMCs was detected using TUNEL assay. The [Ca2+]i in the PASMCs was measured using Fura 2-AM fluorescence. The results showed that the expressions of TRPC6 mRNA and protein, and [Ca2+]i were upregulated under hypoxic and hypercapnic conditions. Hypoxia and hypercapnia promoted cellular proliferation and inhibited apoptosis in the PASMCs. OAG enhanced the above-mentioned effects of hypoxia and hypercapnia, whereas SKF-96365 reversed these effects. These results suggest that TRPC6 may play a role in PASMCs proliferation and apoptosis under hypoxia and hypercapnia by regulating [Ca2+]i.


Assuntos
Apoptose , Hipercapnia/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Canais de Cátion TRPC/metabolismo , Actinas , Animais , Cálcio/metabolismo , Hipóxia Celular , Proliferação de Células , Células Cultivadas , Imidazóis , Masculino , Músculo Liso Vascular/citologia , Artéria Pulmonar/citologia , Ratos , Ratos Sprague-Dawley
10.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 33(5): 415-419, 2017 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926585

RESUMO

OBJECTIVE: To evaluate the effects and mechanism of the Dexmedetomidine on the levels of proinflammatory mediators interleukin 1 beta (IL-1ß) and tumor necrosis factor-α(TNF-α) in ischemia/reperfusion(I/R)rats. METHODS: Fifty healthy SPF male SD rats, 250~310 g,8~12 weeks,were randomly divided into five groups(n=10):sham operation group(sham group),I/R group, dexmedetomidine group(Dex group), atipamezole group(Atip group), dexmedetomidine plus atipamezole(Dex+Atip group). The I/R model was established by clipping hilus of left lung for 30 min and then reperfusion for 2 h. Dex group, Atip group and Dex + Atip group were performed by intraperitoneal injection dexmedetomidine(20 µg/kg),atipamezole(250 µg/kg),Dexmedetomidine(20 µg/kg)+atipamezole(250 µg/kg)respectively 30 min in advance before hilus of left lung was clipped, the rest of the process was the same with I/R group. After the experiment the rats were killed and the left lung tissues to determine the lung wet/dry weight(W/D) and total lung water content(TLW); Ultra structure of lung tissues were observed under light microscope and electron microscope; IL-1ß and TNF-α levels were determined by using ELISA. RESULTS: Compared with the sham group, the W/D、TLW、IL-1ß and TNF-α in other groups were increased significantly (P<0.05). The structure damages of lung tissues observed under light microscope and electron microscope in other groups were more serious than that of sham group. Compared with I/R、Atip、Dex+Atip group, the levels of W/D、TLW,IL-1ß and TNF-α in Dex group were lower (P<0.05), the structure damages of lung tissues observed under light microscopy and electron microscope in Dex group were slighter. There was no significant difference of the above parameters among I/R、Atip、Dex+Atip group. CONCLUSIONS: Dexmedetomidine can alleviate ischemia/reperfusion injury in rat lung through lowering the level of proinflammatory mediators IL-1ß and TNF-α,the possible mechanism may be through stimulation of α2 adrenaline receptors.


Assuntos
Dexmedetomidina/farmacologia , Interleucina-1beta/metabolismo , Pulmão/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Animais , Pulmão/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
11.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 33(1): 47-50, 2017 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926606

RESUMO

OBJECTIVE: To investigate the expression of mRNA and protein of Calcium activated chloride channel (CLCA2) in hypoxic pulmonary artery smooth muscle cell (PASMCs) of rat and it's relationship with ERK1/2 signal pathway. METHODS: PASMCs were randomly divided into 5 groups including normal group(N group), hypoxia group(H group), DMSO group(D group), U0126 group (U group) and Staurosporine aglycone group(SA group). The protein expression of CLCA2 in PASMCs was detected by Western blot.The mRNA expression of CLCA2 was detected by half quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The mRNA and protein expressions of CLCA2 in H group were significantly higher than N group (P<0.01). Comparing with D group,the mRNA and protein expressions of CLCA2 were significantly increased in U group (P<0.01),the mRNA expression of CLCA2 in SA group was obviously decreased (P<0.01) with slightly decreasing of its protein expression. CONCLUSIONS: Hypoxia promotes the expressions of mRNA and protein of CLCA2 in rat PASMCs. The ERK1/2 pathway activator Staurosporine aglycone reduces the mRNA and protein expression of CLCA2 in rats PASMCs and the ERK1/2 pathway inhibitor U0126 induces the upregulation of the mRNA and protein expressiosn of CLCA2 in rats PASMCs.


Assuntos
Canais de Cloreto/metabolismo , Sistema de Sinalização das MAP Quinases , Miócitos de Músculo Liso/metabolismo , Animais , Carbazóis/farmacologia , Hipóxia Celular , Células Cultivadas , Alcaloides Indólicos/farmacologia , Músculo Liso Vascular/citologia , Artéria Pulmonar/citologia , Ratos
12.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 33(4): 380-384, 2017 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926648

RESUMO

OBJECTIVE: To evaluate the effect of dexmedetomidine(Dex) on renal injury induced by lung ischemia/reperfusion(I/R) in mice. METHODS: Fifty healthy SPF male C57BL/6J mice, weighing 20 g~24 g,aged 8~10 weeks,were randomly divided into five groups(n=10 each):sham operation group(sham group),lung ischemia/reperfusion group(I/R group), lung ischemia/reperfusion and normal saline group (NS group), dexmedetomidine group(Dex group), dexmedetomidine and atipamezole group (DA group). Lung ischemia/reperfusion model was established by occlusion of the left pulmonary artery for 30 min followed by 180 min reperfusion in mice. In Dex and DA groups, dexmedetomidine 20 µg/kg and dexmedetomidine 20 µg/kg plus atipamezole 250 µg/kg were injected intraperitoneally respectively at 30 min before establishment of the model, isopyknic normal saline instead of Dex were injected intraperitoneally in NS group. After the experiment the mice were killed and plasma IL-1 beta and tumor necrosis factor α(TNF-α) concentration were detected by ELISA; the renal tissues were harvested to observe ultra structure under electron microscope. RESULTS: Compared with sham group, the concentrations of IL-1ß and TNF-α in other groups were increased significantly and the structure damages of renal tissues observed under electron microscope in other groups were more serious than those of sham group. Compared with I/R group, NS groups and DA group, the concentrations of IL-1ß and TNF-α in Dex group were significantly lower(P<0.05)and the structure damages of renal tissues observed under electron microscope in Dex group were slighter. CONCLUSIONS: Dexmedetomidine pretreatment can attenuate renal injury induced by lung ischemia/reperfusion and the mechanism may be related to inhibition of inflammatory responses.


Assuntos
Dexmedetomidina/farmacologia , Rim/efeitos dos fármacos , Lesão Pulmonar/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Imidazóis , Interleucina-1beta/metabolismo , Rim/lesões , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo
13.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 33(2): 151-155, 2017 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931924

RESUMO

OBJECTIVE: To explore whether yiqi huoxue tongluo jiedu fang (YHTJF, Traditional Chinese Medicine) alleviates the injury during lung ischemia/reperfusion (I/R) in mice through inhibiting oxidative stress or not. METHODS: C57BL/6J male mice (n=70) were randomly divided into 7 groups:control (C), carboxyl methyl cellulose-Na(CMC·Na) + normal control (CC), carboxyl methyl cellulose-Na + sham (CS), carboxyl methyl cellulose-Na + I/R (CIR), carboxyl methyl cellulose-Na + YHTJF-Low, CMC-Na + YHTJF-Middle, CMC-Na + YHTJF-High (CYL, CYM, CYH). The mice in CYL, CYM and CYH group were treated with YHTJF by intraperitoneal injection every day, while the carboxyl methyl cellulose-Na was administered with the same volume of CYL in CC, CS and CIR group. After 3 h-reperfusion, the left lung tissues were harvested to determine the lung wet/dry weight (W/D), the total lung water content (TLW), and the index of quantita-tive evaluation for alveolar damage (IQA). Morphological observation and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) were applied to evaluate the structural changes and the apoptosis index (AI) of the lung tissues. The expressions superoxide of dis-mutase(SOD), malondialdehyde(MDA) and myeloperoxidase(MPO) in the lung tissues were detected by kits. RESULTS: Compared with group C, the W/D, TLW, IQA, AI, lung tissue structural changes, and the expressions of MDA and MPO in group I/R were increased obviously (P < 0.01), and the expression of SOD was decreased, while there was no significant difference between group CC and CS. Compared with group I/R, the parameters of these experiments in group CYL, CYM, CYH were all decreased, and the expression of SOD was increased, while the reduction in group CYM was the most remarkable among them (P < 0.01). CONCLUSIONS: YHTJF may attenuate the I/R injury of the lung by the inhibition of apoptosis via ROS pathway.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Lesão Pulmonar/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose , Pulmão/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Superóxido Dismutase/metabolismo
14.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 33(3): 226-230, 2017 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931937

RESUMO

OBJECTIVE: To explore the relationship between hypoxic pulmonary arterial smooth muscle cells(PASMCs)proliferation, apop-tosis and mitogen-activated protein kinases(MAPK) signal pathway in rats. METHODS: PASMCs were obtained from male SD rats by the enzyme digestion method and primarily cultured; PASMCs were identified through two methods:immunofluorescence staining and light microscopy; the 4~6th generation PASMCs of logarithmic growth state of good growth period were selected, and randomly divided into 7 groups:normoxic con-trol group (N), hypoxia group (H), DMSO group (D), extracellular signal-regulated kinase1/2(ERK1/2) inhibitor-U0126 group (U) and p38MAPK inhibitor-SB203580 group (S), the p38MAPK activator-Anisomycin group (A), the ERK1/2 activator-Staurosporine Aglycone group (SA). When all the models were completed, the all groups joined the CCK-8 to measure cell proliferation; cell apoptosis of each group was detected by TUNEL kit after the modeling. RESULTS: Compared with N group, the expression of OD value in H group was up-regulated (0.990 ±0.041 vs 1.143 ±0.033,P < 0.01). There was no statistical significance on PASMCs apoptosis index(AI) in H group (4.913 ±0.451 vs 5.452 ±0.557, P > 0.05); Compared With H group, there were no statistical significance on the expression of PASMCs OD value and apoptosis index(AI)in D group (1.143 ±0.033 vs 1.142 ±0.049,5.452 ±0.557 vs 5.402 ±0.651,P > 0.05); the expression of OD value in U group was down-regulated, and the expression of AI was up-regulated (1.143 ±0.033 vs 0.985 ±0.078, 5.452 ±0.557 vs 10.145 ±2.545, P < 0.01); the expression of OD value in S group was up-regulated, and the expression of AI was down-regulated (1.143 ±0.033 vs 1.295 ±0.039, 5.452 ±0.557 vs 3.093 ±0.409, P < 0.01); the expression of OD value in A group was down-regulated, and the expres-sion of AI was up-regulated (1.143 ±0.033 vs 0.347 ±0.067, 5.452 ±0.557 vs 25.753 ±1.262, P < 0.01); the expression of OD value in SA group was up-regulated, and the expression of AI was down-regulated (1.143 ±0.033 vs 1.685 ±0.100, 5.452 ±0.557 vs 1.700 ±0.095, P < 0.01). CONCLUSIONS: The regulation of PASMCs' proliferation and apoptosis under hypoxia condition have a relationship with the participation of MAPK signal pathway.


Assuntos
Apoptose , Proliferação de Células , Sistema de Sinalização das MAP Quinases , Miócitos de Músculo Liso/citologia , Animais , Hipóxia Celular , Células Cultivadas , Masculino , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/enzimologia , Artéria Pulmonar/citologia , Ratos , Ratos Sprague-Dawley
15.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 32(5): 408-412, 2016 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931843

RESUMO

OBJECTIVE: To observe the effects of ligustrazine hydrochloride injection(LHI) on pulmonary arterial hypertension in chronic obstructive pulmonary disease(COPD) patients and to investigate its possible mechanisms. METHODS: Twenty-two cases of patients with COPD were randomly divided into conventional treatmentgroup (group C) and ligustrazine treatment group(group L), 11 persons were randomly selected from healthy subjects without lung disease served as normal control group(group N). Group C was given bed rest, low flow oxygen inhalation, bronchial diastolic agent, glucocorticoid and antibiotics and other conventional treatment, and group L was added with ligustrazine hydrochloride injection on the above mentioned basis treatment, group N was given no treatment. After 2 weeks, lung function, blood gas analysis and pulmonary arterial pressure were compared among the three groups, and the content of H2S in plasma was tested with sensitive sulfur electrode method. RESULTS: ①After two weeks treatment, in group L and group C pulmonary function, blood gas analysis, pulmonary artery pressure were obviously improved, and group L was better than group C (P<0.05); ② In group L the content of H2S was increased (P<0.01), group C had no significant difference (P>0.05), and there was a significant difference between the two groups (P<0.01). CONCLUSIONS: Combination with LHI can effectively improve lung function. LHI mayrelieve hypoxic hypercapnia pulmonary hypertension induced by COPD through raising the content of H2S.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/complicações , Pirazinas/uso terapêutico , Humanos , Hipercapnia/tratamento farmacológico
16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 32(2): 164-168, 2016 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931870

RESUMO

OBJECTIVE: To investigate the effect of dexmedetomidine (DEX) on expression of endoplasmic reticulum stress (ERS)-related cysteinyl aspirate specific proteinase-12 (Caspase-12) in lung ischemia/reperfusion (I/R) injury mice. METHODS: Forty C57BL/6J mice were randomly divided into 4 groups:sham operation group (sham group),ischemia/reperfusion injury group (I/R group), normal salinecontrol group (NS group), ischemia/reperfusion + dexmedetomidine group (DEX group). Dexmedetomidine was infused intraperitoneally into the mice to stablish situ left pulmonary I/R injury mouse model. In NS group, the isometric dexmedetomidine was replaced by normal saline,other operations were as the same as the DEX group. After reperfusion 3 hours, the lung tissue wet/dry weight (W/D), the total lung water content (TLW) of the left lung tissues were determined. The lung tissue morphology changes were observed by light microscopy and the damage assessment(IQA) was taken. The structure changes and the apoptosis index (AI) of the lung tissues were evaluated by TUNEL method. The protein and mRNA expression of Caspase-12 and grp78 in lung tissues were detected by Western blot and reverse translate-PCR. RESULTS: Compared with the sham group, the W/D, TLW, IQA, AI, lung tissue structure damages, and the expression of Caspase-12 and grp78 protein and mRNA obviously raised both in I/R group and NS group (P<0.01 or P<0.05). Compared with I/R group, the W/D, TLW, IQA, AI of DEX group were all decreased, the demaged lung tissue morphology changes were significantly reduced, the protein and mRNA expression level of Caspase-12 and grp78 in DEX group were decreased (P<0.01). CONCLUSIONS: DEX can effectively relieve the lung I/R injuries in mice, which maybe associated with inhibition of pneumocyte apoptosis induced by ERS-related Caspase-12 pathway.


Assuntos
Caspase 12/metabolismo , Dexmedetomidina/farmacologia , Estresse do Retículo Endoplasmático , Pulmão/metabolismo , Traumatismo por Reperfusão , Animais , Apoptose , Proteínas de Choque Térmico/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL
17.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 32(2): 173-176, 2016 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931871

RESUMO

OBJECTIVE: To investigate the protective effects of xuebijing (XBJ, Traditional Chinese Medicine Complex) injection on cardiac function in rats with myocardial hypoxia/reoxygenation(H/R) injury. METHODS: The isolated langendorff perfused rat heart model was established. One hundred and thirty SD rats were randomly divided into sham group, hypoxia/reoxygenation group, low dose XBJ(XBJL) group, middle dose XBJ(XBJM) group and high dose XBJ(XBJH) group. All groups except sham group were divided into three subgroups according to reoxygenation time(0.5 h,1 h, 2 h) (n=10). In sham group, left ventricular development pressure(LVDP), maximal rates of increase/decrease of the left ventricular pressure(±dp/dtmax), left ventricular pressure (LVP), and heart rates (HR) were recorded after 20 minutes balance perfusion. The creatine kinase-MB (CK-MB) in myocardium was detected by ELISA. In other groups, after 20 minutes balance perfusion, we perfused ThomasⅡto stop the hearts from beating for 30 minutes, then reperfused the K-H until hearts recover beating. The microstructure of myocardium was observed under light microscopy. LVDP, ±dp/dtmax, LVP and HR were continuously recorded in other four groups and the concentrations of CK-MB in myocardium were measured by ELISA at different time points after reoxygenation. Microstructure of myocardium in each group were observed under light microscopy. RESULTS: LVDP, ±dp/dtmax, LVP and HR of other groups were significantly lower than those of sham group(P<0.05). The levels of CK-MB were higher than that of sham group(P<0.05). LVDP, ±dp/dtmax, LVP and HR of XBJL, XBJM and XBJH groups were higher than those of I/R group at corresponding time points after reoxygenation(P<0.05). The levels of CK-MB were lower than that of I/R group(P<0.05) and the cardiac function was improved. The middle dose of XBJ had the best protective effect. CONCLUSIONS: Xuebijing injection can effectively improve cardiac function and structure in rats with myocardial hypoxia/reoxygenation injury, and middle dose of XBJ is the best.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hipóxia/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley
18.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 32(4): 356-360, 2016 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931961

RESUMO

OBJECTIVE: To investigate the effect of Dexmedetomidine (Dex) on Toll-like receptor 4(TLR4) expression in lung during lung ischemia/reperfusion(I/R) in rats and its possible protecting mechanisms. METHODS: In vivo I/R model in left lung of SD rats was estab-lished. Fifty adult healthy male SD rats were randomly divided into five groups (n=10):control group (Sham group), I/R group, Dex group, atipamezole group (Atip group) and Dex+Atip group. After the I/R experiment,rats were killed and the left lung tissues were harvest-ed to get the lung wet/dry weight(W/D); Ultrastructure of lung tissue were observed under light microscopy; The mRNA expression of TLR4 in lung tissues were determined by RT-PCR; The protein level of TLR4 in lung tissues was detected by Western blot. RESULTS: ①Compared with those in the Sham group, W/D and total lung water content (TLW) in other groups increased significantly (P<0.05), the mRNA and protein expression levels of TLR4 in lung tissues increased too. The structure damages of lung tissues observed under light microscopy in other groups were more than that of Sham group. ②Compared with those in the I/R group, W/D and TLW in the Dex group were lower (P<0.05, P<0.01), the mRNA and protein expression levels of TLR4 in lung tissues decreased (P<0.01), and reduced structure damages of lung tissues were observed under light microscopy in Dex group. ③Compared with those in the Dex group, W/D and TLW in the Dex+Atip group were higher (P<0.01), the mRNA and protein expression levels of TLR4 in lung tissues increased (P<0.01), and the structure damages of lung tissues observed under light microscopy were more serious. There was no significant difference of the above parameters among I/R、Atip、Dex+Atip groups. CONCLUSIONS: Lung ischemia/reperfusion caused high expression of TLR4 and finally induced damages of the lung. Dexmedetomidine could inhibit TLR4 expression and alleviate the lung ischemia/reperfusion injury, which was related to activation of α2-adreno receptor.


Assuntos
Dexmedetomidina/farmacologia , Inflamação/prevenção & controle , Pulmão/metabolismo , Traumatismo por Reperfusão , Receptor 4 Toll-Like/metabolismo , Animais , Pulmão/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley
19.
Artigo em Chinês | MEDLINE | ID: mdl-26016233

RESUMO

OBJECTIVE: To investigate the expression profile of interleuki-1ß (IL-1ß) in rat myocardium at different time points during hypoxia/reoxygenation(H/R)transition. METHODS: The isolated Langendorff perfused rat heart model was established.Forty SD rats were randomly divided into sham group (A group) and hypoxia/reoxygenation group (H/R group). The H/R group rats were subdivided into H/R 0.5 h group(B group), H/R 1 h group(C group), H/R 2 h group(D group)according to reoxygenation time. The left ventricular development pressure(LVDP), maximal rates of increase/decrease of the left ventricular pressure(±dp/dtmax) were continuously recorded. The concentration of interleukin-1ß(IL-lß) and creatine kinase-MB (CK-MB) in myocardium was measured by ELISA. The mRNA expression of IL-lß in myocardium was determined by RT-PCR. Microstructure of myocardium was observed under light microscopy. RESULTS: The value of LVDP and ±dp/dtmax in hypoxia/reoxygenation group rat were significantly lower than that in sham group(P < 0.05). The expression of IL-lß and CK-MB at protein level and the expression of IL-1ß at mRNA level in hypoxia /reoxygenation group were higher than that in sham group(P < 0. 05). There were significant differences of the above parameters among H/R 0.5 h, 1 h, 2 h group(P <0.05). The concentration of IL-1ß and CK-MB, the mRNA expression of IL-1ß were higher in H/R 2 h group than that of other groups(P < 0.05). CONCLUSION: The high expression of IL-Iß in myocardium after myocardial hypoxia /reoxygenation in rats might lead to. ischemia/reperfusion injury.


Assuntos
Hipóxia/metabolismo , Interleucina-1beta/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Animais , Creatina Quinase Forma MB/metabolismo , Modelos Animais de Doenças , Hipóxia/patologia , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 31(5): 418-21, 426, 2015 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-26827533

RESUMO

OBJECTIVE: To explore the effect of ERK1/2 MAPK pathway on the expression of Kv1.5 channel, a voltage-gated potassium ion channel, in rat pulmonary artery smooth muscle cells (PASMCs) and its mechanisms during the process of hypoxia. METHODS: The PASMCs derived from SD rats were cultivated primarily. The third to sixth generation of PASMCs were divided into 5 groups randomly: (1) Normal group (N); (2) Hypoxic group (H); (3) Demethy sulfoxide(DMSO) group (HD); (4) U0126 group (HU): 10 micromol/L U0126; (5) Anisomycin group (HA): 10 micromol/L anisomycin. There were three dishes of cells in each group. The cells in normal group were cultured in normoxic incubator (5% CO2, 37 degrees C), the cells in other groups were added to 0.05% DMSO in the hypoxic incubator (5% CO2, 2% O2, 37 degrees C), all cells were cultured for 60 h. RT-PCR and Western blot were used to detected the espressions of Kv1.5 mRNA and protein in PASMCs. RESULTS: Compared with N group, the expressions of Kv1.5 mRNA and protein in H, HD and HA groups were reduced significantly (P < 0.05); Compared with H group and HD groups, Kv1.5 mRNA and protein expressions in HU group were increased sharply (P < 0.05). Compared with the HU group, Kv1.5 mRNA and protein expressions in HA groups were significantly lower (P < 0.05). CONCLUSION: Low oxygen reduced Kv1.5 mRNA and protein expressions, U0126 could resistant the Kv1.5 channel lower expression caused by hypoxia. Anisomycin had no significant effect on Kv1.5 channel expression under hypoxia, but the expression of Kv1.5 was still significantly lower than the normal oxygen group. These data suggest that hypoxia may cause hypoxic pulmonary hypertension by interfering ERK1/2 signaling pathway to inhibit Kv1.5


Assuntos
Canal de Potássio Kv1.5/metabolismo , Sistema de Sinalização das MAP Quinases , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Animais , Hipóxia Celular , Hipertensão Pulmonar , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Oxigênio , Artéria Pulmonar/citologia , RNA Mensageiro , Ratos , Ratos Sprague-Dawley
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