目的 探讨银杏黄酮(ginkgetin, GK)对心肌缺血再灌注损伤(myocardial ischemia reperfusion injury,MIRI)的保护作用。方法 选取SD大鼠48只,随机分为假手术组、模型组、GK高剂量组(200 mg/kg)、GK低剂量组(100 mg/kg),每组12只。于造模术前1周开始腹腔注射给药;经左冠状动脉结扎45 min再灌注6 h构建MIRI模型,采用NBT染色法测定心肌梗死面积,流式细胞术测定细胞凋亡率,荧光法测定心肌细胞半胱氨酸蛋白酶caspase活性,RT-qPCR法测定心肌凋亡因子Fas、Fas-L基因表达。结果 与模型组比较,GK高、低剂量组可使梗死区面积/危险区面积及梗死区面积/心室总面积显著缩小(P<0.05),可明显降低心肌细胞凋亡率(P<0.01),可显著抑制胞浆caspase-3和caspase-8活性(P<0.05),可使心肌组织Fas和Fas-L基因表达明显降低(P<0.05)。结论 GK预处理对MIRI具有心肌保护作用,可能与影响Fas介导的死亡受体信号途径、抑制心肌细胞凋亡反应等有关。
Abstract
Objective To investigate the protective effects of ginkgetin (GK) on myocardial ischemia reperfusion injury (MIRI) in rats and its effects on cardiomyocyte apoptosis.Methods SD rats were divided randomly into sham, model, GK high dose (200 mg/kg) and GK low dose (100 mg/kg) groups. GK was administered by intraperitoneal injection for 7 days before the model operation. Rat model of MIRI was established by coronary artery ligation for 45 min followed by 360 min reperfusion. After the reperfusion, myocardial infarct area (IA), area at risk (AAR) and left ventricle area (LVA) were measured by the NBT staining. The cardiomyocyte apoptosis rate was detected by flow cytometry. The caspase activities in cardiomyocytes were determined by fluorescence method and cardiomyocyte apoptosis factors (Fas and Fas-L) mRNA expression were examined by RT-qPCR.Results GK (200 and 100 mg/kg) significantly reduced IA/AAR and IA/LVA, compared to those of model group (P<0.05 or P<0.01). The cardiomyocyte apoptosis rates in GK groups were evidently reduced (P<0.01). The intracytoplasmic caspase-3 and caspase-8 activities in GK groups were significantly inhibited (P<0.05 or P<0.01). The Fas and Fas-L mRNA expression in GK groups were evidently reduced, which showed significant differences compared to those of model group (P<0.05).Conclusion GK pretreatment shows protective effect on MIRI, which related to preventing the activation of death receptor signaling pathway and inhibition of cardiomyocyte apoptosis.
关键词
银杏黄酮 /
心肌缺血/再灌注损伤 /
心肌细胞凋亡 /
死亡受体信号途径
Key words
ginkgetin /
myocardial ischemia reperfusion injury /
cardiomyocyte apoptosis /
death receptor signaling pathway
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