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淫羊藿苷对大鼠糖尿病心肌缺血再灌注损伤模型治疗作用及机制研究
淫羊藿苷对大鼠糖尿病心肌缺血再灌注损伤模型治疗作用及机制研究
[摘要] 研究淫羊藿苷(icariin)对大鼠糖尿病心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)模型的治疗作用及可能的机制。通过链脲佐菌素(STZ)复制糖尿病大鼠模型,再通过可逆性左冠状动脉前降支结扎法建立心肌缺血再灌注模型,给予大鼠心肌缺血30 min,再灌注120 min。雄性SD大鼠40只,随机分为5组:对照组(NS)、缺血再灌注组(NIR)、糖尿病对照组(MS)、糖尿病缺血再灌注组(MIR)、糖尿病缺血再灌注淫羊藿苷治疗组(MIRI)。观察血糖、体重和生活状态的变化;检测血清中CK-MB,LDH,GSH-Px及心肌中SOD等酶活性及心肌中MDA和NO含量;HE染色观察心肌病理变化;Western blot法检测心肌中Caspase-3,Bcl-2,Bax蛋白表达。结果显示,糖尿病模型复制成功;糖尿病状态下心肌缺血再灌注损伤更加严重;淫羊藿苷可以通过提高NO水平,减少MDA生成,降低CK-MB和LDH活性、升高SOD和GSH-Px活性,减少Caspase-3及Bax蛋白的表达,增加Bcl-2蛋白的表达,改善心肌受损程度。结果表明,淫羊藿苷可能通过对抗氧化应激及抑制细胞凋亡来发挥糖尿病状态下缺血再灌注心肌损伤的保护作用。
[关键词] 淫羊藿苷;糖尿病;心肌缺血再灌注损伤;氧化应激;凋亡
[Abstract] To study the therapeutic effect and possible mechanism of icariin on myocardial ischemia-reperfusion injury (MIRI) model in diabetes rats. The model of diabetic rats were induced by Streptozotocin (STZ), then the model of MIRI was established by ligating the reversible left anterior descending coronary artery for 30 min, and then reperfusing for 120 min. totally 40 male SD were randomly divided into five groups: the control group (NS), the ischemia reperfusion group (NIR), the diabetes control group (MS), the diabetic ischemia reperfusion group (MIR) and the diabetic ischemia reperfusion with icariin group (MIRI). The changes in blood glucose, body weight and living status were observed; the enzyme activity of serum CK-MB, LDH, GSH-Px and myocardium SOD and the content MDA and NO in myocardium were detected; the myocardial pathological changes were observed by HE staining; the myocardial Caspase-3, the Bcl-2, Bax protein expressions were detected by Western blot. The result showed that the diabetes model was successfully replicated; myocardial ischemia-reperfusion injury was more serious in diabetes rats; icariin can increase NO, SOD, GSH-Px, Bcl-2 protein expression, decrease MDA formation, CK-MB and LDH activities and Caspase-3 and Bcl-2 protein expressions and myocardial damage. The result suggested that icariin may play a protective rol
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