[Retracted] LINC00665 functions as a competitive endogenous RNA to regulate AGTR1 expression by sponging miR­34a­5p in glioma.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the 'Control' data panel shown for the EdU assay experiment in Fig. 6D on p. 1209 was strikingly similar to a data panel featured in Fig. 7 that had already been submitted to the journal Cancer Management and Research by different authors at different research institutes [Chen T­J, Gao F, Yang T, Li H, Li Y, Ren H and Chen M­W: Knockdown of linc­POU3F3 suppresses the proliferation, apoptosis, and migration resistance of colorectal cancer. Cancer Manag Res 12: 4379­4390, 2020]. Owing to the fact that contentious data in the above article had already been submitted for publication prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 1202­1212, 2021; DOI: 10.3892/or.2021.7949].

LINC00665 functions as a competitive endogenous RNA to regulate AGTR1 expression by sponging miR­34a­5p in glioma.

Glioma is the most aggressive tumor of the central nervous system. Long non­coding RNAs (lncRNAs) may be involved in modulating tumor generation. The present study analyzed an lncRNA microarray of glioma and selected long intergenic non­protein coding RNA 665 (LINC00665) as the research object. The mode of expression and biological function of LINC00665 in glioma were assessed using lncRNA microarray and RT­qPCR analyses. Gain­of­function assays and/or loss­of­function assays were implemented to explore the role of LINC00665 in the progression of glioma. Dual­luciferase reporter and RNA immunoprecipitation assays explored the downstream molecular mechanism of LINC00665. The function of the molecular pathway in progression of glioma was analyzed using rescue assays. High expression of LINC00665 was marked in glioma tissues and cells, which correlated with an unsatisfactory prognosis. Upregulation of LINC00665 significantly promoted the proliferation and invasion of glioma cells. LINC00665 acted as a competing endogenous RNA by sponging miR­34a­5p to upregulate angiotensin II receptor type 1 (AGTR1). LINC00665 promoted the progression of glioma by acting as a competitive endogenous RNA to competitively bind to miR­34a­5p and mediate AGTR1 expression.

Fibroblast growth factor 21 attenuates hypoxia-induced pulmonary hypertension by upregulating PPARγ expression and suppressing inflammatory cytokine levels.

Hypoxia-induced pulmonary hypertension (HPH) is a progressive disease characterized by a sustained, elevated pulmonary arterial pressure and vascular remodeling. The latter pathogenesis mainly involves overproliferation of pulmonary artery smooth muscle cells (PASMCs). Fibroblast growth factor 21 (FGF21) has recently emerged as a novel regulator that prevents cardiac hypertrophic remodeling. However, its possible role in pulmonary remodeling remains unclear. The activation of peroxisome proliferator activated receptor γ (PPARγ) is reported to attenuate HPH by suppressing proliferative signals. Loss of PPARγ in the lung contributes to abnormal proliferation of PASMCs. FGF21 is a key regulator of PPARγ activity in adipocytes, but its role has not been elucidated in PASMCs. Therefore, we hypothesized that FGF21 may confer therapeutic effects in HPH by upregulating the expression of PPARγ. Sprague-Dawley rats were exposed to hypoxia and treated with FGF21 for 4 weeks. In parallel, hypoxic conditions and FGF21 were administered to rat PASMCs for 48 h. FGF21 attenuated the hypoxia-induced elevation in mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy (RVH), medial thickening and overproliferation of PASMCs. Furthermore, FGF21 abrogated the reductions in PPARγ expression and increases in TNF-α, IL-1 and IL-6 levels in PASMC culture media. Collectively, these results demonstrate that FGF21 could potentially attenuate the pathogenic derangements of HPH by targeting PPARγ and inflammatory cytokines.

[Effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion induced myocardial injury in mice].

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.

[Effect of dexmedetomidine on apoptosis and CHOP in hypoxia/reoxygenation injury A549 cell].

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.

Acetylshikonin attenuates angiotensin II-induced proliferation and motility of human brain smooth muscle cells by inhibiting Wnt/ß-catenin signaling.

Cerebrovascular smooth muscle cell proliferation and migration contribute to hyperplasia in case of cerebrovascular remodeling and stroke. In the present study, we investigated the effects of acetylshikonin, the main ingredient of a Chinese traditional medicine Zicao, on human brain vascular smooth muscle cell (HBVSMCs) proliferation and migration induced by angiotensin II (AngII), and the underlying mechanisms. We found that acetylshikonin treatment significantly inhibited AngII-induced HBVSMCs proliferation and cell cycle transition from G1 to S phase. Wound-healing assay and Transwell assay showed that AngII-induced cell migration and invasion were markedly attenuated by acetylshikonin. In addition, AngII challenge significantly induced Wnt/ß-catenin signaling activation, as evidenced by increased ß-catenin phosphorylation and nuclear translocation and GSK-3ß phosphorylation. However, acetylshikonin treatment inhibited the activation of Wnt/ß-catenin signaling. Consequently, western blotting analysis revealed that acetylshikonin effectively reduced the expression of downstream target genes in AngII-treated cells, including c-myc, survivin and cyclin D1, which contributed to the inhibitory effect of acetylshikonin on HBVSMCs proliferation. Further, stimulation with recombinant Wnt3a dramatically reversed acetylshikonin-mediated inhibition of proliferation and cell cycle transition in HBVSMCs. Our study demonstrates that acetylshikonin prevents AngII-induced cerebrovascular smooth muscle cells proliferation and migration through inhibition of Wnt/ß-catenin pathway, indicating that acetylshikonin may present a potential option for the treatment of cerebrovascular remodeling.

[The effect of Yiqi Wenyang Huoxue Huatan Fang on hypoxia-hypercarbia induced pulmonary hypertension and its mechanism].

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.

[Excessive endoplasmic reticulum stress mediates brain damage in hypoxia hypercapnia induced pulmonary hypertension rats].

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.

[Effects of Dexmedetomidine on the levels of proinflammatory mediators IL-1ßand TNF-α in pulmonary ischemia/reperfusion injury rats and the mechanisms].

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.

[The role of JNK in apoptosis of renal tubular epithelial cells in diabetic rats with fluctuant high blood glucose].

OBJECTIVE: To explore the signal transduction mechanisms of apoptosis in renal tubular epithelial cells in diabetic rats with fluctuant high blood glucose. METHODS: Healthy SD rats were randomly divided into 3 groups: normal control group (A), stable high blood glucose group (B) and fluctuant high blood glucose group (C). Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg), and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of ordinary insulin and glucose at different time point every day. The superoxide dismutase (SOD) activity and the content of malonaldehyde (MDA) in renal tissue homogenate were detected with colorimetry. The protein expression of Nox4 and JNK were examined by immunohistochemistry and Western blot. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). RESULTS: After 12 experimental weeks, significantly increased cell apoptosis, up-regulation of Nox4 and P-JNK expression in renal tubular epithelial cells were observed in B and C groups compared with those in A group. The MDA content increased and SOD activity decreased in renal tissue in B and C groups. Above effects were more obviously shown in C group. CONCLUSION: Fluctuant high blood glucose induced more apoptosis of renal tubular epithelial cell than stable high blood glucose in diabetic kidney, which might be related to the activation of JNK signal transduction pathway.

[Protective effects and mechanism of SP600125 on lung ischemia/reperfusion injury in rats].

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.

[Effects of Panax notoginseng saponins on pneumocyte apoptosis and c-Jun N-terminal kinase in lung ischemia/reperfusion injury].

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.

[Effects of ambroxol combined with low-dose heparin on TNF-alpha and IL-1beta in rabbits with acute lung injury].

OBJECTIVE: To investigate the intervention and mechanism of ambroxol combined with low-dose heparin on oxidative stress, TNF-alpha and IL-1beta in rabbits with acute lung injury (ALI). METHODS: Twenty-four healthy Japanese rabbits were randomly divided into three groups: (1) Normal saline control group (NC), (2) Oleic acid injury group (OA), (3) Ambroxol + low-dose heparin therapy group (AH). After the success of ALI model, AH group was injected ambroxol + low-dose heparin, while the NC group and OA group were injected the same dose of normal saline by the same method. Arterial oxygen tension (PaO2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) at different time points were determined. The pathological manifestation of both side lungs was observed at the end of expeiment. The activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), xanthine oxidase (XO) and the content of malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) and lung tissue homogenate were tested. The apoptosis index was detected. The lung wet/dry (W/D) ratio was calculated. The pathological changes in lung tissue were observed by light microscopy, and the ultrastructural changes of lung tissue were observed by electron microscopy. RESULTS: (1) The instructive injury induced by ALI observed under electron microscope and light microscope and W/D was decreased significantly in AH group. (2) PaO2 was improved significantly in AH group, compared with that in OA group (P < 0.01). (3) The activity of GSH-Px and SOD in AH group increased significantly (P < 0.01 or P < 0.05) but the activity of XO and the content of MDA decreased significantly (P < 0.01), compared with those in OA group. (4) Except the content of IL-1beta in serum before treatment, the content of IL-1beta and TNF-alpha in serum, BALF, lung tissue homogenate of OA group increased significantly (P < 0.01), and those were obviously improved in AH group. (5) Apoptosis index (AI) in AH group decreased significantly (P < 0.01) compared with that in OA group. CONCLUSION: In ALI induced by OA, IL-1beta and TNF-alpha increases significantly and involved in the occurrence and development of ALI. Ambroxol combined with low-dose heparin can reduce lung cells oxidative stress to inhibit the release of IL-1beta and TNF-alpha, which play a role in the treatment of ALI.

[Effects of cyclosporine A on pneumocyte apoptosis with lung ischemia/reperfusion injury in rats].

OBJECTIVE: To investigate the effects of cyclosporine A (CsA), a powerful inhibitor of mitochondrial permeability transition pore (MPTP), on pneumocyte apoptosis, the release of cytochrome C and the activity of caspase-3 after lung ischemia/reperfusion, and explore the mechanisms. METHODS: Single lung in situ ischemia/reperfusion animal model was used. 30 SD rats were randomly divided into three groups (n = 10): sham (S) group, ischemia/reperfusion (I/R) group and cyclosporine A (CsA) group. Apoptosis of pneumocyte was assessed by TUNEL method, cytochrome C (CytC) in cytoplasm was detected by immunohistochemistry techniques, and the activity of caspase-3 was measured with spectrophotometer. RESULTS: The content of CytC in cytoplasm, the activity of caspase-3, and the value of apoptosis index (AI) in ischemia/reperfusion group were evidently higher than that in S group (P < 0.01). CsA suppressed apoptosis as well as CytC release and caspase-3 activity (P < 0.01). CONCLUSION: CsA can prevent the release of cytochrome C, block the apoptosis of pneumocyte accordingly maybe by closing the MPTP.

[Effect of Shenmai injection on expression and activity of heme oxygenase-1 in reperfusion injury after pulmonary ischemia in rabbits].

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.