五参顺脉胶囊通过抑制内质网应激诱导的凋亡减轻大鼠冠脉侵入性损伤

Wushen-Shunmai capsule attenuates invasive injury of coronary artery by inhibiting endoplasmic reticulum stress-induced apoptosis in rats

目的:探讨五参顺脉胶囊减轻大鼠冠状动脉侵入性损伤的作用和分子机制。方法:采用心肌缺血再灌注损伤模拟大鼠冠状动脉侵入性损伤模型,将大鼠随机分为正常对照组、模型组和五参顺脉胶囊高、中、低剂量治疗组,每组10只。采用2,3,5-氯化三苯基四氮唑染色法检测心肌梗死体积;采用caspase-3/7和caspase-8活性试剂盒检测大鼠心肌梗死区caspase-3/7和caspase-8活性;采用Western blot法检测大鼠心肌梗死区内质网应激标志蛋白转录激活因子4(ATF4)和C/EBP同源蛋白(CHOP)的水平。结果:与正常对照组相比,模型组大鼠心肌梗死体积显著增大,caspase-3/7和caspase-8的活性显著增强,ATF4和CHOP的表达增加(P <0. 05);给予五参顺脉胶囊治疗后,大鼠心肌梗死体积减少,caspase-3/7和caspase-8的活性降低,ATF4和CHOP的表达降低(P <0. 05)。结论:五参顺脉胶囊对缺血再灌注损伤大鼠的心肌具有保护作用,其可能机制与抑制内质网应激所介导的细胞凋亡有关,提示五参顺脉胶囊干预对大鼠冠状动脉侵入性损伤具有一定的治疗作用。

AIM:To explore the effect of Wushen-Shunmai capsule on invasive injury of coronary artery in rats and underlying mechanisms.METHODS:The model of invasive injury of coronary artery in rats was developed by myocardial ischemia-reperfusion injury.The rats were randomly divided into control group,model group and high-dose,middle-dose and low-dose Wushen-Shunmai capsule treatment groups,with 10 rats in each group.The size of myocardial infarction was detected by TTC staining,the activities of caspase-3/7 and caspase-8 were measured by caspase-3/7 and caspase-8 assay kits,and the protein levels of the markers of endoplasmic reticulum stress,activating transcription factor 4(ATF4)and C/EBP homologous protein(CHOP),were examined by Western blot.RESULTS:Compared with control group,the infarct size of myocardium was remarkably increased in model group,the activities of caspase-3/7 and caspase-8 were significantly enhanced,and the protein levels of ATF4 and CHOP were increased(P<0.05).However,compared with model group,after Wushen-Shunmai capsule treatment,the infarct size of myocardium was remarkably decreased,the activities of caspase-3/7 and caspase-8 were significantly weakend,and the protein levels of ATF4 and CHOP were decreased(P<0.05).CONCLUSION:Wushen-Shunmai capsule significantly attenuates ischemia-reperfusion injury in rats.The protective effect may be related to inhibiting endoplasmic reticulum stress-induced apoptosis,suggesting that Wushen-Shunmai capsule has a therapeutic effect on invasive injury of coronary artery.