AIM: To investigate whether excessive endoplasmic reticulum stress (ERS) is involved in the protective mechanism of Panax quinquefolium saponins (PQS) against ischemia/reperfusion (I/R) injury in rat myocardium. METHODS: The model of myocardial I/R injury in vivo was made by ligating the left anterior descending artery for 45 min followed by 24 h of reperfusion in SD rats. The hemodynamics and serum content of cardiac troponin T ( cTnT) were measured. The myocardial infarct size was measured by Evans blue and 2,3, 5-triphenyltetrazolium chloride (TTC) staining. Cardiomyocyte apoptosis was detected using in situ TDT-mediated dUTP nick end labeling (TUNEL). The protein levels of glucose-regulated protein 78 (GRP78) , calreticulin (CRT) , C/EBP homologous protein (CHOP) , caspase-12, apopto-sis-associated proteins Bax and Bcl-2 were determined by Western blotting. RESULTS: Compared with I/R group, the mean arterial pressure in PQR + IR group was decreased by 32. 0% , and left ventricular ± dp/dtmax was increased by 64. 0% and 35. 0% , respectively. The serum content of cTnT was decreased by 53. 3% , the percentage of area of necrosis ( AN)/area at risk (AAR) was reduced by 65.5% and the apoptosis rate was decreased by 54.9%. The myocardial pathological changes were improved. Bcl-2 protein expression was increased by 110. 0% and that of Bax was decreased by 47. 8%. CRT protein expression was decreased by 43. 4 % , CHOP protein expression and the protein level of cleaved caspase-12 were decreased by 38.6% and 23.7% in PQS + I/R group. CONCLUSION: PQS alleviates I/R injury in myocardium by inhibition of excessive ERS.%目的:观察西洋参茎叶总皂苷(PQS)对大鼠心肌缺血/再灌注(ischemia/reperfusion,I/R)损伤的保护作用,并从内质网应激(ERS)的角度探讨其可能的分子机制.方法:采用SD大鼠心肌I/R模型,随机分为正常对照组、模型组与药物预处理组,检测血流动力学及血清心肌肌钙蛋白T (cTnT)含量,以氯化三苯基四氮唑(TTC)和伊文思蓝双染法检测心梗面积,采用HE染色和TUNEL法分别评估心肌病理损伤和心肌细胞凋亡程度,Western blotting法检测心肌组织凋亡调节因子以及内质网应激相关蛋白的表达.结果:与I/R组相比,PQS+ I/R组平均动脉压降低32.0％ (P ＜0.05),左室±dp/dtmax分别升高64.0％和35.0％ (P ＜0.05),血清cTnT含量降低53.3％ (P ＜0.05),坏死面积/缺血面积(AN/AAR)百分比降低65.5％ (P ＜0.05),心肌细胞凋亡率降低54.9％ (P＜0.05)；心肌组织病理损伤程度减轻；抗凋亡蛋白Bc1-2表达升高110.0％ (P ＜0.05),促凋亡蛋白Bax表达降低47.8％ (P ＜0.05),钙网蛋白(CRT)表达降低43.4％ (P ＜0.05),C/EBP同源蛋白(CHOP)和剪切后的caspase-12蛋白表达分别降低38.6％和23.7％ (P ＜0.05).结论:PQS可显著减轻大鼠心肌I/R损伤,其机制与降低I/R诱导的CRT过表达,抑制CHOP、caspase-12等内质网凋亡通路激活,从而抑制过度ERS介导的细胞凋亡有关.
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