降糖舒心方对糖尿病心肌内质网应激c-JNK凋亡旁路的影响

Effect of Jiangtang Shuxin Recipe on Endoplasmic Reticulum Stress c-JNK Apoptosis Pathway in Diabetic Myocardium

目的：探讨降糖舒心方（JTSX）抑制SD糖尿病大鼠心肌细胞内质网应激c-JNK凋亡旁路,减轻糖尿病心肌重构的分子机制。方法：采用高脂饲养＋链脲佐菌素制备2型糖尿病大鼠模型,成模后随机分为模型组、西药组、JTSX低剂量组（JTSX1组）和JTSX高剂量组（JTSX2组）,另设正常组作对照。相应药物干预8周后,检测空腹血糖（FBG）、血脂、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）变化。用透射电镜观察心肌组织超微结构; TUNEL法检测心肌细胞凋亡水平;用RT-PCR和免疫组化分别检测c-JUN氨酸端激酶（c-JNK）和糖调节蛋白78（GRP78）的mRNA转录及其功能蛋白的表达水平。结果：与模型组相比,各给药组均能明显降低FBG（P 〈0. 05）,升高SOD、GSH-Px（P 〈0. 05）;均可降低TG、LDL-C（P 〈0. 05）,升高HDL-C（P 〈0. 05）;均可下调c-JNK、GRP78mRNA转录及其蛋白表达（P 〈0. 05）,降低心肌细胞凋亡指数（AI）（P 〈0. 05）,并改善心肌组织超微结构;与西药组相比,JTSX2疗效更显著（P 〈0. 05）。结论：JTSX能改善糖尿病代谢紊乱,提高抗氧化应激能力,抑制内质网应激细胞凋亡通路,从而改善心肌重构,疗效具有剂量依赖性。

Objecive：To investigate the molecular mechanism of Jiangtang Shuxin（ JTSX） Recipe inhibiting endoplasmic reticulum stress c-JNK apoptotic pathway and reducing myocardial remodeling in SD diabetic rats. Methods： Type 2 diabetes were established in male SD rats by injecting streptozotocin and feeding high lipid diet. After T2 DM models established successfully,the rats were divided into model group,Western medicine group（ Gliquidone ＋ Benazepril）,low-dose JTSX group（ JTSX1） and high-dose JTSXgroup（JTSX2）. Another normal group was used as control group. After 8 weeks of corresponding drug intervention,the levels of fasting blood glucose（ FBG）,serum superoxide dismutase（ SOD）,glutathione peroxidase（ GSH-Px） were measured. The ultrastructure of myocardial tissue was observed with transmission electron microscope. TUNEL was used to detect cardiomyocyte apoptosis. The mRNA and their functional protein levels of c-Jun N-terminal kinases（ c-JNK） and glucose-regulated protein78（ GRP78） were determined by the method of RT-PCR and immunohistochemistry respectively. Results：Compared with model group,after drugs intervention,all administered groups could significantly decrease FPG（ P〈0. 05）,elevate SOD and GSH-Px activity（ P〈0. 05）; all could depress the levels of TG and LDL-C（ P〈0. 05）,and raise HDL-C（ P〈0. 05）;all could cut down the mRNA transcription and their functional protein expression of the c-JNK and GRP78（ P〈0. 05）; all could reduce cardiomyocyte apoptosis index（ AI）（ P〈0. 05） and improve the ultrastructure of myocardial tissue. Compared with Western medicine group,the JTSX2 effect was more significant（ P〈0. 05）. Conclusion：JTSX can improve metabolic disorders in diabetes mellitus,ameliorate the ability of antioxidant stress,suppress endoplasmic reticulum stress apoptosis c-JNK pathway,and therefore improve myocardial remodeling,and the therapeutic effect was dose-dependent.