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目的探讨α-硫辛酸对内质网应激介导的糖尿病大鼠心肌细胞凋亡影响。方法选择SD雄性健康大鼠50只,体重250～300 g,用链脲佐菌素建立糖尿病模型,实验设对照组,糖尿病组,α-硫辛酸低、中、高剂量组(15、30、60 mg/kg灌胃12周),对照组和糖尿病组每日给予等量生理盐水灌胃,测定大鼠血糖、心功能、心脏指数及左心室指数;原位末端转移酶标记技术检测细胞凋亡;western blotting检测葡萄糖调节蛋白78(GRP78)与C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CHOP)的蛋白表达。结果与对照组比较,糖尿病组大鼠血糖[(26.15±4.24)mmol/L]和心功能左室舒张末压(LVEDP)[(9.57±1.16)mm Hg]均升高(P<0.05),右心室收缩压(LVSP)[(62.45±4.10)mm Hg]、±dp/dtmax[(4 502.32±238.92)mm Hg/s]均降低(P<0.05);与糖尿病组比较,α-硫辛酸干预组各指标得到改善;与对照组比较,糖尿病组大鼠心肌细胞凋亡率[(11.28±0.33)%]增加(t=3.875,P<0.05),GRP78与CHOP蛋白表达比值升高;与糖尿病组比较,α-硫辛酸组心肌细胞凋亡率降低,GRP78与CHOP蛋白表达降低(P<0.01)。结论α-硫辛酸对糖尿病大鼠心肌有保护作用,其作用机制可能与内质网应激有关。
Objective To investigate the effects of α-lipoic acid on cardiomyocyte apoptosis induced by endoplasmic reticulum stress in diabetic rats. Methods Fifty SD male healthy rats weighing 250-300 g were used to establish diabetic model with streptozotocin (STZ). The control group, diabetes group, low, medium and high dose of α-lipoic acid group (15, 30, 60 mg / kg for 12 weeks). The rats in the control group and diabetic group were given intragastric administration of normal saline orally, and the blood glucose, cardiac function, cardiac index and left ventricular index of rats were measured. In situ terminal transferase labeling Western blotting was used to detect the protein expression of GRP78 and C / EBP cyclic adenosine monophosphate response element binding transcription factor homologous protein (CHOP). Results Compared with the control group, the blood glucose ([(26.15 ± 4.24) mmol / L] and LVEDP [(9.57 ± 1.16) mm Hg] The mean systolic pressure (LVSP) [(62.45 ± 4.10) mm Hg] and ± dp / dtmax [(4 502.32 ± 238.92) mm Hg / s] were significantly lower than those of the diabetic group Compared with the control group, the apoptosis rate of cardiomyocytes in diabetic rats increased (11.28 ± 0.33)% (t = 3.875, P <0.05) and the ratio of GRP78 to CHOP increased Compared with diabetic group, the apoptotic rate of cardiomyocytes in α-lipoic acid group decreased and the expression of GRP78 and CHOP protein decreased (P <0.01). Conclusion α-lipoic acid has a protective effect on myocardium in diabetic rats and its mechanism may be related to endoplasmic reticulum stress.