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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(P<0.01),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(P<0.05,P<0.01),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。
Objective: To observe the effect of total glucosides of paeony on cell endoplasmic reticulum stress and apoptosis in myocardial ischemia-reperfusion rats and to explore its mechanism. Methods: Sprague-Dawley rats were randomly divided into sham-operation group, ischemia-reperfusion group and low, medium and high dosage of total glucosides of paeony (group Ⅰ, 50,100,200 mg · kg-1 · d-1ig). The changes of cardiac function in each group were observed. The area of myocardial infarction was determined by TTC staining. The expression of glucose regulatory protein in myocardium was detected by Western blot. (GRP78), Caspase-3 and Caspase-12 protein expression of apoptosis-promoting factor CCAAT / enhancer binding protein homologous protein (CHOP), in situ cell apoptosis (TUNEL) method was used to detect apoptosis. Results: Compared with the sham-operation group, the T-wave elevation and left ventricular end-diastolic pressure increased significantly, the left ventricular systolic pressure, left ventricular systolic pressure and diastolic pressure change rate (± dp / dtmax) , The expression of Caspase-12 and Caspase-3 were significantly increased (P <0.01), the area of myocardial infarction and cell apoptosis were obvious. Compared with the ischemia-reperfusion group, total glucosides of paeony decreased T wave elevation in a dose- (P <0.05, P <0.01), reduce the area of myocardial infarction (P <0.05), and increase the left ventricular end-diastolic pressure, increase the left ventricular systolic pressure and left ventricular ± dp / dtmax and decrease the expression of GRP78, CHOP, Caspase-12 and Caspase- And apoptosis. Conclusion: Total glycosides of paeony can improve cardiac function, myocardial infarction and apoptosis after ischemia-reperfusion, which may be related to inhibiting the expression of GRP78, decreasing the levels of CHOP, Caspase-12 and Caspase-3 in myocardial endoplasmic reticulum .