西洋参茎叶总皂苷通过抑制过度内质网应激减轻大鼠心肌缺血/再灌注损伤

 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Bcl-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。

Panax quinquefolium saponins protect rat myocardium from ischemia/reperfusion injury through attenuating excessive endoplasmic reticulum stress

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, apoptosis-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.