白芍总苷对心肌缺血再灌注大鼠心肌细胞内质网应激及凋亡的影响

目的:观察白芍总苷预处理对心肌缺血再灌注大鼠细胞内质网应激及凋亡的影响,并探讨其作用机制。方法:雌性SD大鼠制备大鼠心肌缺血再灌注模型,随机分为假手术组、缺血再灌注组及低、中、高剂量白芍总苷组(造模前分别予以白芍总苷50,100,200 mg·kg-1·d-1ig),观察各组动物心脏功能的变化,三苯基四氮唑(TTC)染色法测定心肌梗死面积,蛋白质免疫印迹(Western blot)检测心肌组织葡萄糖调节蛋白78(GRP78),凋亡促进因子CCAAT/增强子结合蛋白同源蛋白(CHOP)半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)及Caspase-12蛋白表达,原位细胞凋亡检测(TUNEL)方法检测细胞凋亡。结果:与假手术组比较,T波上抬及左心室舒张末期压力明显升高,左心室收缩压、左心室最大收缩期及舒张期压力变化率(±dp/dtmax)明显降低,GRP78,CHOP,Caspase-12,Caspase-3蛋白表达明显升高(P0.01),心肌梗死面积及细胞凋亡明显;与缺血再灌注组比较,白芍总苷呈剂量依赖性的降低T波上抬及左心室舒张末期压力,升高心脏左心室收缩压、左心室±dp/dtmax,降低GRP78,CHOP,Caspase-12,Caspase-3蛋白表达(P0.05,P0.01),减少心肌梗死面积及细胞凋亡。结论:白芍总苷能改善缺血再灌注的心功能、心肌梗死及凋亡,作用可能是与抑制心肌内质网应激相关蛋白GRP78表达,下调CHOP,Caspase-12,Caspase-3水平有关。

Effects of Total Glucosides From Paeoniae Radix Albae on Endoplasmic Reticulum Stress and Apoptosis in Myocardial Ischemia Reperfusion Rats

Objective: To investigate the effects of total glucosides from Paeoniae Radix Alba (TGP) on endoplasmic reticulum stress and apoptosis in myocardial ischemia reperfusion rats. Method: Female Sprague-Dawley rats were used to establish myocardial ischemia reperfusion models and randomly divided into sham operation group, ischemia reperfusion (I/R) group, TGP low-dose group (ig 50 mg · kg^-1 · d^-1), TGP middle-dose group (ig 100 mg · kg^-1 · d^-1), and TGP high-dose group (ig 200 mg · kg^-1 · d^-1). Changes of cardiac function were observed in various groups; myocardial infarction size was detected by triphenyltetrazolium chloride (TTC) staining; levels of myocardial glucose regulating protein78(GRP78), CCAAT/EBP homologous protein (CHOP), Caspase-12 and Caspase-3 protien expression were measureed by Western blot; the apoptotic cardiomyocytes were assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). Result: As compared with the sham operation group, T-wave elevation and LVEDP were significantly increased; LVSP and +dp/dt_max were significantly reduced; and the protein expression levels of GRP78, CHOP, Caspase-12, and Caspase-3 were significantly increased in I/R group (P<0.01), with obvious myocardial infarction size and cells apoptosis. As compared with I/R group, T-wave elevation and LVEDP were reduced; LVSP and +dp/dt_max were increased; and the protein expression levels of GRP78, CHOP, Caspase-12 and Caspase-3 were reduced (P<0.05, P<0.01) in TGP groups in a concentration-dependent manner, with reduced myocardial infarction size and cells apoptosis. Conclusion: TGP can improve the cardiac function, myocardial infarction and apoptosis in myocardial ischemia reperfusion rats, and its mechanism may be associated with inhibiting the expression levels of GRP78, CHOP, Caspase-12 and Caspase-3.