不同剂量梓醇对大鼠缺血心肌的保护作用

目的探讨梓醇预处理对大鼠在体心肌缺血再灌注的保护作用及其机制。方法实验动物选用健康成年SD大鼠88只,雌雄不限,体重250～300g。采用结扎大鼠左冠状动脉前室间支的方法制备心肌缺血再灌注模型。实验动物随机分为6组,分别为假手术组（n=8）、模型组（n=16）、阳性药物组（n=16）及梓醇低剂量组（1mg/kg,n=16）、中剂量组（5mg/kg,n=16）、高剂量组（10mg/kg,n=16）。各用药组在缺血前7天连续腹腔给药,对照组注射等量生理盐水。测各组大鼠心肌梗死面积,同时用黄嘌呤氧化酶法测定心肌组织的超氧化物歧化酶活性和用硫代巴妥酸法测定丙二醛含量;Tunel法观察心肌细胞凋亡;免疫组化检测凋亡蛋白Bax、Bc1-2、Caspase-3蛋白质表达。结果梓醇组梗死面积明显小于模型组（P〈0.01）;梓醇组心肌组织超氧化物歧化酶明显高于模型组（P〈0.05）,丙二醛酶值明显低于模型组（P〈0.05,P〈0.01）;Tunel法检测示梓醇组心肌细胞凋亡指数明显低于模型组（P〈0.01,P〈0.05）,Bcl-2蛋白免疫阳性细胞明显多于模型组（P〈0.05）,Bax、Caspase-3免疫阳性细胞明显少于模型组（P〈0.05,P〈0.01）。且上述指标在梓醇3个剂量组间比较呈剂量依赖型变化,剂量越高,作用越显著。结论梓醇对缺血再灌注损伤的心肌具有保护作用,其机制可能与其增强抗氧化酶活性,减少自由基对心肌的氧化损伤,抑制细胞凋亡有关。

Protective effect of different dose of Catalpol Preconditioning on ischemiareperfusion injured myocardium in rats

【Objective】To investigate the protective effect and the probable mechanisms of different dose of catalpol on ischemia-reperfusion injured myocardium at rat heart in vivo.【Methods】A total of 88 adult,healthy,Sprague Dawley rats,with body weight of 250~300g were selected.Myocardial ischemia/reperfusion injury model was established by ligating the anterior interventricular branch of the left coronary artery,all animals were randomLy divided into sham operation（n=8）,ischemia/reperfusion model（n=16）,positive group（n=16）and catalpol 1 mg/kg（n=16）,5 mg/kg（n=16） and 10 mg/kg（n=16）.The drug groups were once a day treated i.p.with relevant drug a week before occlusion,and the sham and model were given i.p.the same does saline.The area of myocardial infarction was measured by tetrazolium chloride staining;malondialdehyde（MDA） was measured by thiobarbiturate colorimetry,and superoxide dismutase（SOD） activity was detected by xanthine oxidase technique;cardiomyocyte apoptosis was detected by TdT mediate dUTP nick end labeling（TUNEL）assay,and theprotein expression of Bcl-2,Bax and Caspase-3 in myocardium were assayed by immunochemistry.【Results】Compared with ischemia/reperfusion group,the area of myocardial infarction in catalpol groups decreased（P 0.01）.The level of MDA was obvious decreased in the catalpol groups（P0.05）,the content of SOD were significantly higher than that in ischemia/reperfusion group（P0.05,P0.01）.The apoptotic index of catalpol groups reduced significantly by Tunel compared with model（P0.01,P0.05）.The expression of Bcl-2 was enhanced,while the expressions of Bax and Caspase-3 were depressed by catalpol.All the outcomes of caltalpol groups were taken on in a dose-dependent manner.【Conclusion】Catalpol preconditioning has some protective effect against ischemia/reperfusion,and the protective mechanism may be achieved by improving free radicals and myocardial metabolism,inhibiting myocardial apoptosis.