白芍总苷对心肌缺血再灌注大鼠内质网应激因子CHOP、GRP78、GRP94的表达及凋亡的影响

目的:研究白芍总苷(TGP)对心肌缺血再灌注(I/R)大鼠内质网应激因子CCAAT/增强子结合蛋白的同源蛋白(CHOP)、葡萄糖调节蛋白78(GRP78)、葡萄糖调节蛋白94(GRP94)表达及凋亡的影响。方法:选择健康清洁级SD大鼠75只,根据随机数字表法分成5组,每组15只,分别记为假手术组、I/R组、50 mg/kg TGP组、100 mg/kg TGP组以及200 mg/kg TGP组。检测并对比各组大鼠CHOP、GRP78、GRP94水平,对比分析各组大鼠心肌I/R指标、梗死面积率以及心肌细胞的凋亡率。结果:I/R组和TGP各组的CHOP、GRP78及GRP94水平均明显高于假手术组,且TGP各组较I/R组明显更低(均P0.05)。100 mg/kg和200 mg/kg TGP组的CHOP、GRP78及GRP94水平均明显低于50 mg/kg TGP组,且200 mg/kg TGP组较100 mg/kg TGP组明显更低(均P0.05)。I/R组和TGP各组缺血30 min的T波改变、再灌注120 min的T波改变及LVEDP水平均明显高于假手术组,LVSP、+dp/dtmax及-dp/dtmax水平均明显低于假手术组(均P0.05)。与I/R组相比,TGP组缺血30 min的T波改变、再灌注120 min的T波改变及LVEDP水平呈剂量依赖型下降,而LVSP、+dp/dtmax及-dp/dtmax水平呈剂量依赖型上升(均P0.05)。I/R组和TGP各组的梗死面积率和心肌细胞的凋亡率均明显高于假手术组(均P0.05)。与I/R组相比,TGP组的梗死面积率和心肌细胞的凋亡率水平呈剂量依赖型下降(均P0.05)。结论:应用TGP能够明显降低MIRI大鼠内质网应激因子CHOP、GRP78、GRP94的表达,调节心肌缺血和再灌注相关标志物或临床参数的水平,显著减少心肌缺血和再灌注所致的心肌梗死面积率及细胞凋亡率。

Effects of Total Glucosides of Paeony on Expression and Apoptosis of Endoplasmic Reticulum Stress Factors CHOP, GRP78, GRP94 in Rats with Myocardial Ischemia Reperfusion Injury

ABSTRACT Objective: To study the effects of total glucosides of paeony (TGP) on the expression and apoptosis of endoplasmic reticulum stress factor CCAAT/ enhancer binding protein homologous protein (CHOP), glucose regulated protein 78 (GRP78), glucose regulated protein 94 (GRP94) in rats with myocardial ischemia reperfusion (I/R) injury. Methods: 75 health clean SD rats were selected and divided into 5 groups according to the digital random list method, with 15 rats in each group, which were recorded as sham operation group, I/R group, 50 mg/kg TGP group, 100 mg/kg TGP group and 200 mg/kg TGP group. The levels of CHOP, GRP78, GRP94 in the rats of each group were detected and compared. The indexes of myocardial I/R, the infarct area rate and the apoptosis rate of myocardial cells of each group were compared and analyzed. Results: The levels of CHOP, GRP78 and GRP94 in the I/R group and TGP group were significantly higher than those in the sham operation group, and those were significantly lower in the I/R group than each group of TGP(all P<0.05). The levels of CHOP, GRP78 and GRP94 in 100 mg/kg group and 200 mg/kg TGP group were significantly lower than those in 50 mg/kg TGP group, and those were significantly lower in the 200 mg/kg TGP group than in the 100 mg/kg TGP group(all P<0.05). In the I/R group and each group of TGP, the T-wave changes in 30 min after ischemia, T-wave changes in 120 min after reperfusion and LVEDP level were higher than those in the sham operated group, while the levels of LVSP, +dp/dtmax and -dp/dtmax were significantly lower than those in the sham operated group(all P<0.05). Compared with the I/R group, the T-wave changes in 30 min after ischemia,T-wave changes in 120 min after reperfusion and LVEDP level decreased in a dose-dependent manner, while the levels of LVSP, +dp/dtmax and -dp/dtmax increased in a dose-dependent manner (all P<0.05). The infarct size and myocardial apoptosis rate in I/R group and each group of TGP were significantly higher than those in sham operated group(all P<0.05). Compared with the I/R group, the infarct size and myocardial apoptosis rate of the TGP group decreased in a dose-dependent manner (all P<0.05). Conclusion: TGP can significantly reduce the expression of endoplasmic reticulum stress factors CHOP, GRP78 and GRP94 in MIRI rats, and can adjust the indexes or the level of related markers of myocardial ischemia and reperfusion,and also can effectively reduce the infarct area rate and myocardial cell apoptosis rate.