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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 effect of ginsenoside Rg1 on ischemic / reperfusion arrhythmia in rats and its primary mechanism. Methods: The rat model of ischemic / reperfusion arrhythmia was established. Wistar rats were divided into 5 groups: ischemia / reperfusion group (I / R group) and sham operation group (SO group) The rats in the low-dose group (Rg1-L group) were injected intraperitoneally with 20 mg · kg -1 · d -1 ginsenoside Rg1 and the high dose ginsenoside Rg1 group (Rg1-H group) kg -1 d -1 ginsenoside Rg 1, and the positive control group was given intraperitoneal injection of 20 mg · kg -1 d -1 metoprolol succinate week. The change of electrocardiogram was observed. The severity of arrhythmia was analyzed by arrhythmia score. The area of myocardial infarction after ischemia / reperfusion was determined by TTC staining. The mRNA expression of Bax and Bcl-2 in cardiomyocytes was detected by qRT-PCR. The protein expression levels of Cleaved-PARP, Cleaved-caspase-9 and Cleaved-caspase-3 in cardiomyocytes were detected by Western blot. Results: Occurrence of ventricular premature ventricular contraction (PVC) and ventricular tachycardia (VT) were observed in SO group, Rg1-L group, Rg1-H group and MS group; PVC, VT and ventricular fibrillation (VF). The arrhythmia scores of SO, I / R, Rg1-L, Rg1-H and MS groups were 0.37, 4.2, 1.9, 0.46 and 0.42, respectively. The results of TTC staining showed that the ratio of infarct area to ischemic area in I / R group was significantly higher than that in SO group, while the Rg1-L group, Rg1-H group and MS group were significantly lower than those in I / R group (all P <0.05). Compared with I / R group, the expression of Bcl-2mRNA and Bcl-2 protein in the Rg1-L and Rg1-H groups were significantly decreased, and the levels of Bcl-2 mRNA, Cleaved-PARP, Cleaved-caspase-9 and Cleaved-caspase- The performance in the Rg1-H group was more pronounced. CONCLUSION: Ginsenoside Rg1 can significantly reduce the incidence of ischemic / reperfusion arrhythmia and decrease the area of myocardial infarction in rats. The mechanism may be through the regulation of endogenous mitochondrial apoptotic pathway.