Fan Hongyan, Li Mingyue, Shen Ze, Jiang Chang, Cui Xiaoli, Wang Min, Zhou Jingjing, Sun Yu, Li Saizeng, Wang Yanchun
Department of Pharmacology, College of Basic Medicine, Jilin Medical University, Jilin 132013, China.
College of Clinical Medicine, Jilin Medical University, Jilin 132013, China.
Wei Sheng Yan Jiu. 2020 Jan;49(1):98-131. doi: 10.19813/j.cnki.weishengyanjiu.2020.01.017.
To study the effect of curcumin on the expression of glucose regulated protein 78 kD(GRP78) and cysteinyl aspartate specific proteinase-12(caspase-12) of myocardial endoplasmic reticulum stress related factors in type 2 diabetes rats.
Type 2 diabetes rats model was established by high-fat drink feeding and one-time intraperitoneal injecting streptozotocin(35 mg/kg). After model rats were built, rats was randomly divided into diabetic model group and low dose of curcumin group(200 mg/kg), high dose of curcumin group(400 mg/kg) and captopril group(60 mg/kg) with 10 rats in each group. The rats in each group were ig administered with corresponding drugs once a day. Continuous administration for 12 w. The levels of fasting blood glucose(FBG) and lactate dehydrogenase(LDH), electrocardiogram and heart weight index(HWI) were measured respectively. The myocardial pathological changes were observed by HE staining. The levels of collagen fiber expression in myocardial tissue were performed by Masson staining. The protein expression levels of GRP78 and caspase-12 in myocardium of rats were observed by immunohistochemistry.
The result showed that compared with control group, the levels of FBG and LDH of serum were increased obviously, HWI was increased, myocardial cells were hypertrophy, the collagen fibers of intercellular space of cell were increased, the protein expressions of GRP78 and caspase-12 of myocardium were increased in rats, myocardial cell apoptosis was increased in the model group(P<0. 05). Compared with model group, FBG and LDH levels and HWI were reduced, the collagen fiber of intercellular space were decreased, the protein expression levels of GRP78 and caspase-12 were lowered in high dose of curcumin group(P<0. 05).
It indicates that Cur defends myocardium tissue in type 2 diabetes rats, which may be related to decreasing the level of blood glucose and the protein expressions of GRP78 and caspase-12, and blocking the ERS-initiated apoptotic.
研究姜黄素对2型糖尿病大鼠心肌内质网应激相关因子葡萄糖调节蛋白78kD(GRP78)和半胱天冬酶-12(caspase-12)表达的影响。
采用高脂饮食喂养并一次性腹腔注射链脲佐菌素(35mg/kg)建立2型糖尿病大鼠模型。造模成功后,将大鼠随机分为糖尿病模型组、低剂量姜黄素组(200mg/kg)、高剂量姜黄素组(400mg/kg)和卡托普利组(60mg/kg),每组10只。各组大鼠每天灌胃给予相应药物1次,连续给药12周。分别检测空腹血糖(FBG)、乳酸脱氢酶(LDH)水平、心电图及心脏重量指数(HWI)。通过HE染色观察心肌病理变化。采用Masson染色检测心肌组织中胶原纤维表达水平。通过免疫组化观察大鼠心肌中GRP78和caspase-12蛋白表达水平。
结果显示,与对照组相比,模型组大鼠血清FBG和LDH水平明显升高,HWI增加,心肌细胞肥大,细胞间质胶原纤维增多,心肌GRP78和caspase-12蛋白表达增加,心肌细胞凋亡增加(P<0.05)。与模型组相比,高剂量姜黄素组FBG、LDH水平及HWI降低,细胞间质胶原纤维减少,GRP78和caspase-12蛋白表达水平降低(P<0.05)。
表明姜黄素对2型糖尿病大鼠心肌组织具有保护作用,可能与降低血糖水平、下调GRP78和caspase-12蛋白表达、阻断内质网应激引发的凋亡有关。