银杏叶提取物诱导血红素氧合酶-1表达抗缺血再灌注损伤后心肌细胞凋亡的研究_药学论文.docVIP

银杏叶提取物诱导血红素氧合酶-1表达抗缺血再灌注损伤后心肌细胞凋亡的研究_药学论文 银杏叶提取物诱导血红素氧合酶-1表达抗缺血再灌注损伤后心肌细胞凋亡的研究_药学论文 【关键词】 银杏叶提取物；,,血红素氧合酶-1；,,再灌注损伤；,,凋亡 　　摘要：目的探讨银杏叶提取物（EGb761）诱导血红素氧合酶-1（HO-1）表达抗缺血再灌注损伤（IRI）后心肌细胞凋亡的效果及其机理。方法48只兔随机均分为单纯IRI组、EGb761组、EGb761+ZnPPⅨ组，分别预先给予等容积的生理盐水，EGb761，EGb761+ZnPPⅨ腹腔内注入。24 h后，每组任选8只处死，检测心肌细胞内HO-1表达及活性，余兔结扎冠脉左前降支使心肌缺血40 min，再灌注4 h，取缺血心肌检测中性粒细胞浸润、丙二醛（MDA）含量、Bax蛋白与Bcl-2蛋白表达及心肌细胞凋亡指数（AI）。结果与单纯IRI组及EGb761+ZnPPⅨ组比较，EGb761组HO-1表达及活性均明显升高，中性粒细胞浸润及MDA含量明显降低，Bax 增加而Bcl-2降低，心肌细胞AI显著减少(均为0.01)。与单纯IRI组比较，EGb761+ZnPPⅨ组HO-1表达增加但活性降低(0.05)，MDA含量明显升高(0.05)，其余指标均无显著差异。结论EGb761能明显诱导心肌细胞内HO-1表达，并通过HO-1的抗炎、抗氧化等作用下调Bax表达，上调Bcl-2表达，从而显著抑制IR损伤后心肌细胞凋亡。 　　关键词：银杏叶提取物； 血红素氧合酶-1； 再灌注损伤； 凋亡 　　Abstract：ObjectiveTo explore the protective effects and mechanism of heme oxygenase-1 (HO-1) expression induced by extract of Ginkgo biloba(EGb761) against cardiomyocyte apoptosis from ischemia reperfusion injury(IRI).Methods48 rabbits were randomly divided into simple IR group, EGb761 group and EGb761+ ZnPPⅨ group. Each rabbit in different groups was intraperitoneal injected with saline(5ml), EGb761(10mg/kg), EGb761(10mg/kg)+ ZnPPⅨ(7.5mg/kg) respectively. 24 hours later, 8 rabbits in each group were killed to measure myocardial HO-1 expression and HO-1 activity. Other rabbits were subjected for 40min of myocardial ischemia by ligation of left anterior descending coronary artery followed by 4h of reperfusion. The neutrophil infiltration, myocardial malonaldehyde(MDA) content, Bax and Bcl-2 protein expression, cardiomyocyte apoptosis index(AI) in ischemia areas were detected.ResultsCampared with simple IRI group and EGb761+ ZnPPⅨ group, the expression and activity of myocardial HO-1 increased significantly, the neutrophil infiltration and MDA content decreased. Bax expression increased and AI and Bcl-2 level decreased in EGb761 group(0.01 respectively). Compared with simple IRI group, EGb761+ ZnPPⅨ group showed higher myocardial HO-1 expression but lower HO-1 activity (0.01), while the MDA content increased (