ST-1灌胃抗大鼠心肌缺血再灌注损伤作用及机制初探

发布时间：2018-09-07 21:33

【摘要】： 目的:本实验研究ST-1灌胃预处理对麻醉大鼠心肌缺血再灌注损伤的保护作用,对其作用机制进行初步探讨,并与甜菊苷6种衍生物进行药效学的比较。方法:健康成年大鼠(300±50g)随机分成伪手术组、模型对照组、ST-1预处理组、冠心丹参片预处理组和甜菊苷衍生物组,每组12只,药物在心肌缺血前60 min灌胃给予。大鼠开胸后结扎左冠状动脉前降支30 min再通90 min以形成缺血再灌注模型。连续观察各组鼠动态血流动力学指标:MBP、LVSP、LVDP’、LVEDP和±dp/dtmax等,并记录心律失常(室速,VT和室颤,VF)情况;测定生物化学指标:再灌注末血清乳酸脱氢酶(LDH)和肌酸激酶(CK)的活性;观察心肌组织形态学变化,并用免疫组化方法测定核因子κB(NFκB)、Bcl-2和环氧酶2(COX-2)的活性。结果:大鼠心肌缺血再灌注可引起心功能、生化和组织学损伤。ST-1 2.5、5.0 mg·kg-1灌胃和冠心丹参片200 mg·kg-1灌胃预处理可有效减轻缺血再灌注引起的心功能损伤。ST-1组和冠心丹参片组左室舒缩功能指标均明显高于缺血再灌注模型对照组;心率和血压变化与模型对照组间无显著性差异;缺血再灌注期VT和VF发生率、再灌注末血清LDH和CK活性均明显低于模型对照组对应值。心肌光镜观察表明:ST-1组心肌组织形态学损伤明显轻于模型对照组,并显示与ST-1剂量相关。免疫组织化学观察表明:ST-1组心肌组织的NFκB和COX-2的表达活性明显低于模型对照组,而Bcl-2的表达活性明显高于模型对照组。本实验尚不能证实我校自行合成的6种甜菊苷系列衍生物灌胃预处理具有相似于ST-1的抗心肌缺血再灌注损伤作用。结论:本实验证实ST-1灌胃与静脉注射预处理具有一致的抗麻醉大鼠心肌缺血再灌注损伤作用,该作用可能与抗炎、抗心肌细胞凋亡有关。
[Abstract]:Aim: to study the protective effect of ST-1 preconditioning on myocardial ischemia-reperfusion injury in anesthetized rats and its mechanism, and to compare its pharmacodynamics with 6 kinds of stevioside derivatives. Methods: healthy adult rats (300 卤50 g) were randomly divided into sham operation group, model control group, Guanxin Danshen tablet preconditioning group and stevioside derivative group, 12 rats in each group. The model of ischemia reperfusion was established by ligating the anterior descending branch of the left coronary artery for 90 min after thoracotomy. LVEDP and 卤dp/dtmax were observed continuously, and the activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum were measured at the end of reperfusion, and the arrhythmias (ventricular tachycardia VT and ventricular fibrillation VF) were recorded, and serum lactate dehydrogenase (LDH) and creatine kinase (CK) were measured at the end of reperfusion. The changes of myocardial histomorphology were observed and the activities of NF- 魏 B (NF 魏 B, Bcl-2 and cyclooxygenase-2 (COX-2) were determined by immunohistochemical method. Results: myocardial ischemia-reperfusion induced cardiac function in rats. The indexes of left ventricular systolic and diastolic function in the myocardial ischemia reperfusion group and Guanxin Danshen tablet group were significantly higher than those in the ischemic reperfusion model group and the Guanxin Danshen tablet group and Guanxin Danshen tablet group, respectively. There was no significant difference in heart rate and blood pressure between the model group and the model control group, but the incidence of VT and VF during ischemia-reperfusion and the activities of serum LDH and CK at the end of reperfusion were significantly lower than those in the model control group. Myocardial light microscopy showed that the myocardial histomorphologic damage in the group of w ST-1 was significantly less than that in the model control group and was correlated with the dose of ST-1. Immunohistochemical observation showed that the expression of NF 魏 B and COX-2 in the myocardium of the group of w ST-1 was significantly lower than that of the model control group, while the activity of Bcl-2 was significantly higher than that of the model control group. This experiment can not confirm that the preconditioning of 6 kinds of stevioside derivatives has similar effects on myocardial ischemia-reperfusion injury as ST-1. Conclusion: this study demonstrated that ST-1 administration and intravenous preconditioning had the same effect on myocardial ischemia-reperfusion injury in anesthetized rats, which might be related to anti-inflammation and anti-apoptosis of cardiomyocytes.
【学位授予单位】：东南大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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