白芍总苷对糖尿病大鼠心肌氧化应激和细胞凋亡的影响及机制研究

Effects of total glucosides of paeony on myocardial oxidative stress and apoptosis in diabetic rats

目的探讨白芍总苷(total glucosides of paeony,TGP)对糖尿病大鼠心肌氧化应激和细胞凋亡的影响及其机制。方法取120只SD大鼠按随机数字表法分为对照组、模型组、二甲双胍(Met,200 mg/kg)组和TGP低、中、高剂量(50、100、200 mg/kg)组,每组20只;采用一次性ip链脲佐菌素(65 mg/kg)制备糖尿病大鼠模型;造模后连续8周每天1次ig给药,对照组和模型组同步ig给予生理盐水。通过血糖仪检测空腹血糖水平;生化分析法检测血清乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、丙氨酸氨基转移酶(ALT)含量和心肌组织丙二醛(MDA)含量、抗氧化酶——超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性;通过HE染色、TUNEL染色观察心肌病理学改变和细胞凋亡;Western blotting法检测心肌组织GRP78、CHOP、Cleved Caspase-12蛋白表达。结果与模型组比较,Met组和TGP中、高剂量组大鼠空腹血糖水平显著降低,血清LDH、CK-MB、ALT水平和心肌组织MDA含量显著降低,心肌组织SOD、GSH-Px活性显著升高,心肌组织病理损伤和细胞凋亡状况明显改善、凋亡指数(AI)显著降低,心肌组织GRP78、CHOP、Cleved Caspase-12蛋白表达显著下调,差异有统计学意义(P<0.05、0.01)。结论 TGP对糖尿病大鼠心肌氧化应激和细胞凋亡具有抑制作用,其机制可能与提高抗氧化酶活性和抑制内质网应激凋亡通路有关。

Objective To investigate the effect of total glucosides of paeony(TGP) on myocardial oxidative stress and apoptosis in diabetic rats and its mechanism. Methods Tatolly 120 SD rats were randomly divided into control group, model group, metformin group(70 mg/kg) and TGP low-, medium-and high-dose groups(50, 100 and 200 mg/kg). The diabetic rat models were prepared by ip injection of streptozotocin(65 mg/kg). After the model was established, the drugs were given by gavage simultaneously, once a day for eight weeks, while the rats in the control group and model group were given normal saline. The fasting blood glucose level was detected by blood glucose meter, the content of LDH, CK-MB, ALT in serum and the content of MDA, the activity of ntioxidant enzyme(SOD, GSH-Px) in myocardial were etected by biochemical analysis;The pathological changes and apoptosis of myocardium were observed by HE staining and TUNEL staining;The expression of GRP78, CHOP, Cleved Caspase-12 protein in myocardial tissue was detected by Western blotting method. Results Compared with model group, the fasting blood glucose levels of rats in metformin group and TGP medium-, high-dose groups were significantly decreased;the content of LDH, CK-MB, ALT in serum and MDA in myocardial were significantly decreased, and the activity of SOD, GSH-Px in myocardial were significantly increased;the pathological damage and apoptosis of myocardial tissue were significantly improved, the AI was significantly decreased;the expression of GRP78, CHOP, Cleved Caspase-12 were significantly down-regulated;the differences were significant(P < 0.05 or 0.01). Conclusion TGP has inhibitory effect on myocardial oxidative stress and apoptosis in diabetic rats, and its mechanism may be related to increasing antioxidant enzyme activity and inhibiting endoplasmic reticulum stress apoptosis pathway.