摘要
目的:探讨人参皂苷Rg1对大鼠缺血性/再灌注心律失常的作用及其初步机制。方法:构建大鼠缺血性/再灌注心律失常模型,Wistar大鼠分为5组:缺血/再灌注组(I/R组)与假手术组(SO组)不给予药物,人参皂苷Rg1低剂量组(Rg1-L组)术前腹腔注射20mg·kg^(-1)·d^(-1)人参皂苷Rg1,人参皂苷Rg1高剂量组(Rg1-H组)术前腹腔注射40mg·kg^(-1)·d^(-1)人参皂苷Rg1,阳性对照组(MS组)腹腔注射20mg·kg^(-1)·d^(-1)琥珀酸美托洛尔,共两周。观察大鼠心电图变化,运用心律失常评分分析心律失常的严重程度,采用TTC染色法测定缺血/再灌注后心肌梗死面积;qRT-PCR法检测心肌细胞中Bax与Bcl-2的mRNA表达变化;Western blot检测心肌细胞中凋亡相关蛋白Cleaved-PARP、Cleaved-caspase-9与Cleaved-caspase-3的蛋白表达水平。结果:SO组、Rg1-L组、Rg1-H组与MS组可见偶发室性期前收缩(PVC)与室性心动过速(VT);I/R组可见频发PVC、VT与心室颤动(VF)。SO组、I/R组、Rg1-L组、Rg1-H组及MS组心律失常评分分别为0.37、4.2、1.9、0.46及0.42。TTC染色结果显示,I/R组梗死区与缺血区面积比值显著大于SO组,而Rg1-L组、Rg1-H组、MS组显著小于I/R组(均P<0.05)。与I/R组比较,Rg1-L组和Rg1-H组心肌细胞Bcl-2mRNA表达水平升高,Bax mRNA与Cleaved-PARP、Cleaved-caspase-9与Cleaved-caspase-3蛋白表达水平降低,且在Rg1-H组中表现更加明显。结论:人参皂苷Rg1可明显减少大鼠缺血性/再灌注心律失常的发生率,并减少心肌梗死面积,其机制可能为通过调控内源性线粒体凋亡途径而发挥作用。
Objective：To investigate the effects of Ginsenoside Rgl on arrhythmias following ischemic/reperfu- sion injury in rats and the related mechanism. Method： The myocardial ischemia/reperfusion injury model rats were divided into sham-operated group （SO group）, ischemia/reperfusion group （I/R group）, Ginsenoside Rgl with low dose group （Rg3-L, 20 mg· kg^-1·d^-1 , ip）, Ginsenoside Rgl with high dose group （Rg3-H, 40 mg· kg^-1· d^-1 , ip） and metroprolol succinate group （MS group, 20 mg· kg^-1· d^-1 , ip）. The severity of arrbythmia was judged by arrhythmias scores and the myocardial infarction area was investigated by TTC staining method. The mRNA expressions of Bax and Bcl-2 were determined by qPCR. The expressions of Cleaved-PARP, （＇leaved- caspase 9 and Cleaved-caspase-3 were determined by Western blot. Result： There were occasional occurrences of premature ventricular contraction （PVC） and ventricular tachycardia （VT） in SO, Rgl-L, Rgl-H and MS group, while frequent occurrences of PVC, VT and ventricular fibrillation （VF） in I/R group. The ischemic arrhythmia score in SO, I/R, Rgl L, Rgl-H and MS group was 0.37, 4.2, 1.9, 0.46 and 0.42, respectively. TTC stating showed that, the myocardial infarct size in I/R group was obviously increased compared with SO group, while ob viously decreased in Rgl-L, Rgl-H and MS group compared with I/R group （all P^0.05）. Compared with I/R group, the expression levels of Bcl-2 mRNA increased while Bax mRNA, Cleaved-PARP, Cleaved caspase 9 Cleaved caspase-3 protein decreased in Rgl L and Rgl-H group, the phenomenon was more obvious in Rgl-H group. Conclusion： Ginsenoside Rgl could significantly improve the occurrence ratio of arrhythmias and the myo cardial infarct size after ischemia/reperfusion injury, the mechanism may be related to the regulation of regulate endogenous mitochondrial apoptosis pathway.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2017年第5期465-469,共5页
Journal of Clinical Cardiology
