RESUMO
BACKGROUND: 3% chloroprocaine (CP) has been reported as the common local anesthetic used in pregnant women undergoing urgent cesarean delivery during labor analgesia period. However, 0.75% ropivacaine is considered a promising and effective alternative. Therefore, we conducted a randomized controlled trial to compare the effectiveness and safety of 0.75% ropivacaine with 3% chloroprocaine for extended epidural anesthesia in pregnant women. METHODS: We conducted a double-blind, randomized, controlled, single-center study from November 1, 2022, to April 30, 2023. We selected forty-five pregnant women undergoing urgent cesarean delivery during labor analgesia period and randomized them to receive either 0.75% ropivacaine or 3% chloroprocaine in a 1:1 ratio. The primary outcome was the time to loss of cold sensation at the T4 level. RESULTS: There was a significant difference between the two groups in the time to achieve loss of cold sensation (303, 95%CI 255 to 402 S vs. 372, 95%CI 297 to 630 S, p = 0.024). There was no significant difference the degree of motor block (p = 0.185) at the Th4 level. Fewer pregnant women required additional local anesthetics in the ropivacaine group compared to the chloroprocaine group (4.5% VS. 34.8%, p = 0.011). The ropivacaine group had lower intraoperative VAS scores (p = 0.023) and higher patient satisfaction scores (p = 0.040) than the chloroprocaine group. The incidence of intraoperative complications was similar between the two groups, and no serious complications were observed. CONCLUSIONS: Our study found that 0.75% ropivacaine was associated with less intraoperative pain treatment, higher patient satisfaction and reduced the onset time compared to 3% chloroprocaine in pregnant women undergoing urgent cesarean delivery during labor analgesia period. Therefore, 0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period. CLINICAL TRIAL NUMBER AND REGISTRY URL: The registration number: ChiCTR2200065201; http://www.chictr.org.cn , Principal investigator: MEN, Date of registration: 31/10/2022.
Assuntos
Analgesia Obstétrica , Anestésicos Locais , Cesárea , Procaína , Ropivacaina , Humanos , Feminino , Ropivacaina/administração & dosagem , Gravidez , Método Duplo-Cego , Cesárea/métodos , Anestésicos Locais/administração & dosagem , Adulto , Analgesia Obstétrica/métodos , Procaína/análogos & derivados , Procaína/administração & dosagemRESUMO
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 , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Substâncias Protetoras/farmacologiaRESUMO
Background: Previous studies have explored the median effective concentration (EC50) of ropivacaine for labor epidural analgesia in parturients with obesity. However, the clinical relevance of the 90% effective concentration (EC90) remains unclear. This study aimed to determine and compare the dose-response curve of epidural ropivacaine for labor analgesia between parturients with and without obesity. Methods: Parturients were divided into two groups based on body mass index (BMI): group N, consisting of parturients with BMI <30 kg/m2, and group O, consisting of parturients with BMI >30 kg/m2. Within each group, the patients were randomized to receive one of five concentrations (0.0375%, 0.075%, 0.1125%, 0.15%, or 0.1875%) of epidural ropivacaine for labor analgesia. Analgesia was induced with a loading dose of 15 mL of the assigned concentration. Visual analogue scale (VAS) scores were recorded at baseline and 30 min post-dose to calculate the response (%) using the formula [(baseline VAS pain score-VAS pain score at 30 min)/baseline VAS pain score] ×100%. The EC50 and EC90 values were determined via nonlinear regression analysis. Results: The EC50 and EC90 values of ropivacaine were 0.061% (95% confidence interval [CI], 0.056%-0.066%) and 0.177% (95% CI, 0.152%-0.206%) in group N and 0.056% (95% CI, 0.051%-0.061%) and 0.161% (95% CI, 0.138%-0.187%) in group O, respectively. No significant differences were observed in the EC50 and EC90 values between the two groups (p-values = 0.121 and 0.351, respectively. Conclusion: In conclusion, within the parameters of this study, our findings suggest that obesity, characterized by a mean BMI value of 30.9, does not significantly influence the EC50 and EC90 values of epidural ropivacaine for labor analgesia. Further investigations are warranted to elucidate the dose-response relationship between ropivacaine and obesity with higher BMI values. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=190747, Identifier ChiCTR2300073273.
RESUMO
The aim of the present study is to investigate the effects of Panax notoginseng saponins (PNS) on pneumocyte apoptosis and apoptosis-related protein, as well as c-Jun N-terminal kinase (JNK) in lung ischemia/reperfusion (I/R) injury. Thirty Wistar rats were randomly divided into control group, I/R group and PNS group. The unilateral lung I/R model was replicated by obstruction of left lung hilus for 30 min and reperfusion for 120 min in vivo. The rats in PNS group were given intraperitoneal injection of PNS at 60 min before ischemia and 10 min before reperfusion. Some lung tissues sampled at the end of the experiment were assayed for wet/dry weight ratio (W/T). The expressions of phosphorylated JNK (p-JNK) and JNK protein were detected by Western blot. The expressions of Bcl-2, Bax and Caspase-3 protein were detected by immunocytochemistry techniques. The pneumocyte apoptotic index (AI) was detected by terminal deoxynuleotidy1 transferase mediated dUTP nick end labeling (TUNEL). The morphological and ultrastructure changes were observed under light microscope and electron microscope, and the injured alveolus rate (IAR) was counted as well. The results showed that compared to control group, I/R group showed increased expressions of p-JNK, Bcl-2, Bax and Caspase-3 protein (all P < 0.01), decreased ratio of Bcl-2/Bax (P < 0.05), and increased values of AI, W/T and IAR (all P < 0.01). Moreover, light microscope and electron microscope showed serious morphological and ultrastructure injury in I/R group. Compared to I/R group, PNS group showed markedly decreased expressions of p-JNK, Bax and Caspase-3 protein (all P < 0.01), increased expression of Bcl-2 protein and ratio of Bcl-2/Bax (both P < 0.01), and lower values of AI, W/T and IAR (all P < 0.01). Meanwhile, light morphological and ultrastructure injury was found to be alleviated in PNS group. These results suggest that PNS can protect lung tissue from I/R injury, and the mechanism may correlate with suppressing JNK signal pathway, up-regulating the ratio of Bcl-2/Bax which results in inhibition of Caspase-3 dependent apoptosis.
Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Pulmão/irrigação sanguínea , Panax notoginseng/química , Traumatismo por Reperfusão/prevenção & controle , Saponinas/farmacologia , Animais , Feminino , Isquemia/fisiopatologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Ratos , Ratos Wistar , Saponinas/isolamento & purificação , Transdução de Sinais/efeitos dos fármacosRESUMO
The present study aimed to evaluate the cardioprotective effects of a Rhokinase inhibitor, Y27632, and the underlying mechanisms. A rat model of myocardial ischemiareperfusion (I/R) injury was generated by ligation of the coronary artery, and global ischemia of isolated rat hearts was conducted using the Langendorff system. Staining with triphenyltetrazolium chloride (TTC) and hematoxylin and eosin was performed to analyze the myocardial infarct size and histopathological alterations of the I/Rinduced rat heart. In addition, coronary flow, myocardial contractility and an electrocardiogram were analyzed. The effects of Y27632 on inflammatory cytokines and cardiac enzymes in the serum were assessed by ELISA. The expression of apoptosis and inflammationassociated proteins was also analyzed via western blotting. Rats in the Y27632 group exhibited alleviated myocardial I/R injury according to TTC staining and histopathological diagnosis. Additionally, Y27632 restored the ST segment. The data of coronary flow and myocardial contractility in isolated rat hearts indicated that Y27632 improved heart function following I/R. The levels of inflammatory cytokines and cardiac enzymes in the serum were downregulated by Y27632. The mitogenactivated protein kinase (MAPK) and nuclear factor (NF)κB signaling pathways were inhibited by Y27632. Furthermore, apoptosisassociated protein expression in rats and the isolated hearts was effectively inhibited by Y27632. In conclusion, the findings of the present study indicated that Y27632 attenuated myocardial injury via inhibiting the activation of the MAPK and NFκB signaling pathways; thus, apoptosis and the inflammatory response were suppressed.
Assuntos
Amidas/farmacologia , Amidas/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Piridinas/uso terapêutico , Quinases Associadas a rho/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Citocinas/sangue , Mediadores da Inflamação/metabolismo , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/enzimologia , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismoRESUMO
OBJECTIVE: To explore the effect of Shenmai injection the expression of heme oxygenase-1 (HO-1) in rabbits with reperfusion injury after pulmonary ischemia. METHOD: Single lung ischemia/reperfusion injury animal model was used in vivo. Twenty rabbits were randomly divided into two groups (n = 10, in each), pulmonary ischemia and reperfusion injury (PIRI) group and I-R + Shenmai injection group. The tissue slides were stained by in situ hybridization (ISH) for HO-1 to detect the expression of HO-1 in lung and to analyze the absorbance. Wet to dry ratio of lung tissue weight (W/D) and the injured alveoli rate (IAR) were measured at 180 minutes after lung reperfusion. Meanwhile the lung tissue slide was prepared for electron microscopic observation at 180 minutes after reperfusion. RESULT: HO-1 expression was upregulated in two groups in the pulmonary endothelial cells, part of pulmonary vascular smooth muscle cells, extima of vessels and epithelial cells of airway, the absorbance was 0.148 +/- 0.013, 0.158 +/- 0.012, respectively. The Shenmai injection group showed higher absorbance than those of the IRI group (P < 0.01), lower W/D and IAR values than those of the IRI group (P < 0.01) significantly and lighter abnormal changes of the lung tissue in morphologically than those of the PIRI group. CONCLUSION: Shenmai injection possesses notable protective effects on PIRI in rabbits by increasing the expression of HO-1 in lung.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Animais , Modelos Animais de Doenças , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Ativação Enzimática/efeitos dos fármacos , Feminino , Imuno-Histoquímica , Injeções , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Coelhos , Distribuição AleatóriaRESUMO
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 â ¡ 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 CHOPãglucose-regulated protein of molecular weight 78 kDa (Grp78)ãcysteinyl aspirate-specificprotease-3 (caspase-3) protein and CHOPãGrp78 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 , Chaperona BiP do Retículo Endoplasmático , HumanosRESUMO
To explore the effects of captopril on calpainmediated apoptosis of myocardial cells and cardiac function in diabetic rats, 30 adult male SpragueDawley rats were randomly divided into three groups: Negative control (NC group), untreated diabetic rats (DM group) and diabetic rats treated with captopril (Cap group). Diabetes was induced by streptozotocin injection. Captopril was intragastrically administered at a daily dose of 50 mg/kg for 12 weeks; the NC and DM groups received an equivalent volume of saline. After 12 weeks of treatment, left ventricular systolic pressure (LVSP), left ventricular enddiastolic pressure (LVDEP), maximal rate of left ventricular pressure increase (+dp/dtmax), maximal rate of left ventricular pressure decrease (dp/dtmax) and left ventricular mass index (LVMI) were measured. The levels of calpain1, calpain2, Bcell lymphoma (Bcl)2, Bcl2 associated protein X (Bax) and total caspase3 were detected in cardiac tissue by western blot analysis. The apoptotic index (AI) was assessed with a terminal deoxynucleotidyl transferasemediated dUTP nickend labeling assay. The ultrastructure of cardiac tissue was determined by transmission electron microscopy. Compared with the NC group, LVDEP and LVMI were increased, whereas LVSP, +dp/dtmax and dp/dtmax were decreased in the DM group. In the Cap group, LVDEP and LVMI were decreased, whereas LVSP, +dp/dtmax and dp/dtmax were increased compared with the DM group. Bcl2 protein expression was decreased, whereas the levels of calpain1, calpain2, Bax and total caspase3 protein were increased in the DM group, compared with the NC group. Cap treatment increased Bcl2 protein expression and decreased calpain1, calpain2, Bax and total caspase3 protein expression compared with the DM group. Additionally, the AI was increased in the DM group compared with the NC group, and decreased in the Cap group compared with the DM group. Furthermore, ultrastructural examination demonstrated that myocardial cell injury was reduced in the Cap group compared with the DM group. Therefore, captopril improved myocardial structure and ventricular function, by inhibiting calpain1 and calpain2 activation, increasing Bcl2 expression, reducing Bax expression and subsequently inhibiting caspase3dependent apoptosis.
Assuntos
Captopril/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Coração/efeitos dos fármacos , Disfunção Ventricular Esquerda/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Calpaína/efeitos adversos , Calpaína/genética , Caspase 3/genética , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/patologia , Proteína X Associada a bcl-2/genéticaRESUMO
Previous studies have shown that increasing estradiol concentrations had a toxic effect on the embryo and were deleterious to embryo adhesion. In this study, we evaluated the physiological impact of estradiol concentrations on endometrial cells to reveal that serum estradiol levels probably targeted the endometrium in controlled ovarian hyperstimulation (COH) protocols. An attachment model of human choriocarcinoma (JAr) cell spheroids to receptive-phase endometrial epithelial cells and Ishikawa cells treated with different estradiol (10-9 M or 10-7 M) concentrations was developed. Differentially expressed protein profiling of the Ishikawa cells was performed by proteomic analysis. Estradiol at 10-7 M demonstrated a high attachment rate of JAr spheroids to the endometrial cell monolayers. Using iTRAQ coupled with LC-MS/MS, we identified 45 differentially expressed proteins containing 43 significantly upregulated and 2 downregulated proteins in Ishikawa cells treated with 10-7 M estradiol. Differential expression of C3, plasminogen and kininogen-1 by Western blot confirmed the proteomic results. C3, plasminogen and kininogen-1 localization in human receptive endometrial luminal epithelium highlighted the key proteins as possible targets for endometrial receptivity and interception. Ingenuity pathway analysis of differentially expressed proteins exhibited a variety of signaling pathways, including LXR/RXR activation pathway and acute-phase response signaling and upstream regulators (TNF, IL6, Hmgn3 and miR-140-3p) associated with endometrial receptivity. The observed estrogenic effect on differential proteome dynamics in Ishikawa cells indicates that the human endometrium is the probable target for serum estradiol levels in COH cycles. The findings are also important for future functional studies with the identified proteins that may influence embryo implantation.
Assuntos
Endométrio/metabolismo , Estradiol/sangue , Indução da Ovulação , Western Blotting , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Estradiol/farmacologia , Feminino , Humanos , Mapas de Interação de Proteínas , Proteômica , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismoRESUMO
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 , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVE: To investigate the effects of angiotensin converting enzyme inhibitor (ACEI) captopril on Calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats. METHODS: Thirty adult male SD rats were randomly divided into 3 groups (n = 10), normal control group (NC group), diabetes mellitus group (DM group)and captopril treated group (Cap group). Streptozocin (STZ) were used to make the model of diabetes mellitus, captopril was administrated by gavage at the dose of 50 mg/kg every day, while in NC group and DM group the same volume of normal saline was administrated. Twelve weeks later, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVDEP), maximal rise rate of left ventricular pressure (+ dp/dtmax) and maximal fall rate of left ventricular pressure (- dp/dtmax) were detected; Western blot was used to detect the expression of Calpain-1 Calpain-2, Bcl-2, Bax and total Caspase3 protein; apoptosis index (AI) were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: Compared with NC group, LVDEP was significantly higher; LVSP, + dp/dtmax and - dp/dtmax were significantly decreased (P < 0.05); Bcl-2 protein expression was decreased; the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were increased; the value of AI was significantly increased. Compared with DM group, LVDEP was significantly lower; LVSP, + dp/dtmax and - dp/dtmax were significantly increased (P < 0.05); Bcl-2 protein expression was increased, the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were decreased; the value of AI was significantly decreased (P < 0.05). CONCLUSION: Captopril can protect diabetic myocardial structure through inhibiting activation of Calpain-1 and Calpain-2, up-regulating the expression of Bcl-2, down-regulating the expression of Bax to inhibit Caspase3 dependent apoptosis, thereby improving the ventricular function and myocardial structure.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Animais , Apoptose/efeitos dos fármacos , Calpaína/metabolismo , Cardiomiopatias/patologia , Caspase 3/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Masculino , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To investigate the protective effects and mechanism of SP600125-specificity inhibitor of c-Jun N-terminal kinase (JNK)on lung ischemia /reperfusion injury in rats. METHODS: The unilateral lung ischemia/reperfusion model was replicated in vivo. Rats were randomly divided into three groups (n = 10): control group, ischemia/reperfusion group ( I/R group) and ischemia/reperfusion + SP600125 group (SP600125 group). The lung tissues sampled at the end of each experiment were assayed for wet/dry weight ratio (W/D),the injured alveoli rate (IAR), the expression of phosphorylation JNK (p-JNK) and JNK protein were detected by Western blot, the expression of Bcl-2, Bax, Caspase3 protein were detected by immunocytochemistry techniques, the pneumocyte apoptosis index (AI) was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end abeling(TUNEL), the ultrastructure changes were observed under electron microscope. RESULTS: Compared to I/R group, the expression of p-JNK, Bcl-2, Bax and caspase-3 protein were markedly decreased (all P < 0.01), the expression of Bcl-2 protein and the ratio of Bcl-2/Bax were markedly increased in SP600125 group(all P < 0.01). The value of AI, W/D, IAR showed significantly lower than those in I/R group (all P <0.01). Meanwhile, light morphological and ultrastructure injury were found in SP600125 group. CONCLUSION: SP600125 can suppress JNK signal pathway, up-regulate the ratio of Bcl-2/Bax to inhibit Caspase-3 dependent apoptosis, so that it protects lung tissue from ischemia/reperfusion injury.