芦丁对大鼠心肌缺血再灌注损伤的保护作用及机制研究

发布时间：2018-11-09 08:40

【摘要】：目的探讨芦丁对大鼠心肌缺血再灌注损伤保护作用及机制。方法雄性SD大鼠随机分为5组:假手术组(sham组)、缺血再灌注损伤模型组(MI/RI组)、芦丁高剂量组(RH组80mg/kg)、芦丁中剂量组(RM组40mg/kg)、芦丁低剂量组(RL组20mg/kg),每组10只,建立心肌缺血再灌注损伤模型,芦丁治疗组于术前30分钟灌胃给药。心肌缺血再灌注后超声心动图评估心功能:FS%、EF%;导管法测定血流动力学指标:心率(HR)、左心室舒张末压(LVEDP)、左心室收缩压(LVSP)、左心室舒张最大上升/下降速率(±LVd P/dtmax);染色法测定心肌梗死面积及计算心肌梗死程度;酶标仪检测血清及组织心肌酶生成量(CK-MB、LDH、AST)和氧化指标活性(ROS、SOD、还原型GSH、MDA);HE染色观察组织细胞形态;免疫印迹法(Western Blot)检测Prx II及凋亡相关蛋白Bcl-2、Bax、Caspase-3和Caspase-9的表达。结果与假手术组比较,模型组EF%、FS%显著降低、LVEDP显著升高、LVSP及±LVd P/dtmax显著降低,差异均具有统计学意义(P0.01);心肌酶显著升高(P0.01);ROS与MDA生成量显著升高、SOD与GSH活力/浓度显著降低(P0.01);凋亡蛋白表达增高及抗凋亡蛋白表达降低(P0.01);Prx II表达显著降低(P0.01)。与模型组比较,芦丁治疗组EF%、FS%显著升高、LVEDP显著降低、LVSP及±LVd P/dtmax显著升高,差异均具有统计学意义(P0.01,0.05),呈剂量依赖性;心肌梗死面积显著缩小,心肌梗死程度降低(P0.01,0.05,呈量依赖性;血清心肌酶谱异常变化得到不同程度改善,呈剂量依赖性;ROS与MDA生成量降低、SOD与GSH活力/浓度升高(P0.05,0.01),呈剂量依赖性;凋亡蛋白表达减少及抗凋亡蛋白表达增多(P0.01),Prx II表达显著升高(P0.01),呈剂量依赖性。结论芦丁可以剂量依赖性的减少心肌缺血再灌注损伤模型大鼠的心肌梗死面积、改善心功能,对缺血后复灌的心肌发挥保护作用,其机制可能与芦丁促进心肌内Prx II的表达,提高SOD活力,发挥抗氧化作用,进而抑制心肌细胞凋亡相关。
[Abstract]:Objective to investigate the protective effect and mechanism of rutin on myocardial ischemia reperfusion injury in rats. Methods male SD rats were randomly divided into five groups: sham-operated group (sham group), ischemia-reperfusion injury model group (MI/RI group), rutin high dose group (80mg/kg), and RM group (40mg/kg). Low dose of rutin (20mg/kg) group (10 rats in each group) was used to establish myocardial ischemia-reperfusion injury model. Rutin treatment group was administered intragastrically 30 minutes before operation. Echocardiographic Evaluation of Cardiac function after Myocardial Ischemia reperfusion: FS%,EF%; Left ventricular end-diastolic pressure (HR), left ventricular systolic pressure (LVEDP), left ventricular systolic pressure (LVSP), left ventricular diastolic maximum ascending / descending rate (卤LVd P/dtmax); The myocardial infarction size was measured by staining and the myocardial infarction degree was calculated. The serum and tissue myocardial enzyme production (CK-MB,LDH,AST) and the activity of oxidation index (ROS,SOD, reduced GSH,MDA) were detected by enzyme marker. The expression of Prx II and apoptosis-related proteins (Bcl-2,Bax,Caspase-3 and Caspase-9) were detected by HE staining and Western blot (Western Blot). Results compared with the sham-operated group, the EF%,FS%, LVEDP, LVSP and 卤LVd P/dtmax in the model group were significantly lower than those in the sham-operated group (P0.01), the difference was statistically significant (P0.01), the myocardial enzyme was significantly increased (P0.01). The production of ROS and MDA increased significantly, the activity / concentration of SOD and GSH decreased significantly (P0.01), the expression of apoptotic protein increased and the expression of anti-apoptotic protein decreased (P0.01); Prx II). Compared with the model group, the EF%,FS%, LVEDP, LVSP and 卤LVd P/dtmax in the rutin treatment group were significantly higher than those in the model group. The difference was significant in a dose-dependent manner. The area of myocardial infarction decreased significantly (P 0.01) and the degree of myocardial infarction decreased in a dose-dependent manner, and the abnormal changes of serum myocardial enzymes were improved in a dose-dependent manner. The production of ROS and MDA decreased, and the activity / concentration of SOD and GSH increased in a dose-dependent manner. The expression of apoptotic protein decreased and the expression of anti-apoptotic protein increased (P0.01), Prx II increased significantly (P0.01) in a dose-dependent manner. Conclusion Rutin can decrease myocardial infarction size, improve cardiac function and protect myocardium from reperfusion injury in a dose-dependent manner. The mechanism of rutin may promote the expression of Prx II in myocardium. Increasing the activity of SOD, exerting antioxidant effect, and then inhibiting cardiomyocyte apoptosis.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R54

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