褪黑素对糖尿病大鼠线粒体保护机制的研究

目的 探讨褪黑素(melatonin,MT)对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病大鼠线粒体功能的影响及其机制.方法 STZ诱导糖尿病大鼠模型,将糖尿病大鼠随机分为糖尿病组和褪黑素干预组(褪黑素组),并以正常组作对照.干预8周后,观察各组大鼠心脏、肝脏及肾脏线粒体膜电位和肿胀度的变化,并通过免疫组化法分析线粒体外膜上的电压依赖性阴离子通道(voltage-dependent anion channel,VDAC)蛋白的表达.结果 (1)与糖尿病组比较,褪黑素组心脏、肝脏、肾脏膜电位均明显升高,分别为[(553.6±193.5)mV对(311.4±133.7)mV,P＜0.05]、[(745.7±115.8)mV对(358.9±158.7)mV,P＜0.05]、[(951.6±246.1)mV对(425.8±177.9)mV,P＜0.05];(2)与糖尿病组比较,褪黑素组心脏、肝脏、肾脏肿胀度趋势明显增强;(3)与糖尿病组比较,褪黑素组心脏、肝脏、肾脏VDAC表达均明显增加,分别为(76.93±8.263对58.59±7.62,P＜0.05)、(50.69±6.33对40.11±6.30,P＜0.05)、(77.86±8.59对61.44±12.86,P＜0.05).结论 褪黑素保护糖尿病大鼠心脏、肝脏及肾脏线粒体功能,初步推测可能与上调线粒体VDAC蛋白的表达有关.

Protective effect of melatonin on mitochondria in diabetic rats

Objective To explore the effect of melatonin on mitochondria in streptozotocin (STZ)-induced diabetic rats and its potential mechanism. Methods The diabetic rat models were induced by intraperitoneal injection of STZ, and the diabetic rats were randomly divided into two groups: diabetes mellitus group (DM group) and melatonin-treated group (DM± MT group). The normal non-diabetic rats were served as control group. Mitochondrial membrane potential and mitochondrial swelling were measured, the expression of voltage-dependent anion channel (VDAC)was assayed by immunohistochemistry in the heart, liver and kidney among the different groups after 8 weeks. Results (1)Compared with DM group, mitochondrial membrane potential in the heart,liver and kidney were significantly elevated in DM± MT group (553.6± 193.5 vs. 311.4 ± 133.7;745.7±115.8 vs. 358.9±158.7; 951.6±246.1 vs. 425.8±177.9, all P＜0.05). (2)Compared with DM group, mitochondrial swelling in the heart, liver and kidney was reinforced in DM ± MT group. (3)Compared with DM group, the expressions of VDAC in the heart, liver and kidney were significantly up-regulated in DM± MT group (76.93 ± 8.263 vs. 58.59 ± 7.62, 50.69 ± 6.33 vs.40.11±6.30, 77.86±8.59 vs. 61.44± 12.86, all P＜0.05). Conclusions Melatonin has protective effect on the activity of mitochondria in the heart, liver and kidney in diabetic rats possibly by up-regulating the expression of VDAC.