褪黑素对糖尿病大鼠肾脏病变的保护作用

目的 探讨褪黑素对实验性糖尿病大鼠肾脏病变的保护作用及其机制。方法 将实验动物随机分为正常对照组（C组）、糖尿病组（D组）及糖尿病褪黑素治疗组（M组）。给予褪黑素治疗4周。检测血糖、血肌酐、肾脏肥大指数（肾重／体重），放免法测定24h尿白蛋白排泄量，对肾脏标本进行光镜观察，用图像分析仪测量各组大鼠平均肾小球面积、平均肾小球体积。同时用实时荧光定量RT-PCR法对糖尿病大鼠肾皮质转化生长因子β1（TGF-β1）mRNA表达进行半定量分析。结果 褪黑素治疗组较糖尿病组24h尿白蛋白排泄量、肾脏肥大指数均明显下降（P〈0.05）。实时荧光定量RT-PCR检测糖尿病大鼠肾脏皮质TGF-β1 mRNA表达明显高于正常对照组，为C组的9．2倍，给予褪黑素治疗后，糖尿病大鼠TGF-β1 mRNA表达水平下降3．95倍，但仍明显高于正常对照组（P〈0.01）。肾小球平均面积、平均肾小球体积M组显著低于D组（P〈0.01）。结论 褪黑素可抑制糖尿病大鼠肾脏皮质TGF-β1mRNA表达，减少糖尿病大鼠的尿白蛋白，减轻及延缓肾小球硬化，发挥保护肾脏的作用。

Renal protective effect of melatonin in diabetic rats

Objectives] To investigate the mechanism of melatonin in protecting the renal lesion of diabetic rats.Methods] Experimental diabetic rats were induced by peritoneal injection of streptozotocin. The rats were randomly divided into following groups: normal control rats (group C), streptozotocin-induced diabetic rats (group D) and diabetic rats treated with melatonin (group M). After 4 weeks, the serum creatinine, kidney hypertrophy index (kidney weight/body weight ratio), and 24 h urinary albumin excretion rate were measured, respectively. TGF-β1 mRNA expression in renal cortex of rats using newly real-time quantitative RT-PCR with SYBR Green I and the kidney samples were observed with light microscope, mean glomerular transverse sectional area (MGA) and mean glomerular volume (MGV) were also calculated by analysis system of the image. Results] After 4 weeks, kidney hypertrophy index and 24 h urinary albumin excretion of melatonin treatment group were significantly lower than those in diabetic group D (P ＜0.01). TGF-β1 mRNA expression levels revealed a 9.2-fold increase in diabetic glomeruli after four weeks compared to normal glomeruli (P ＜0.01). While melatonin treatment decrease 3.95-fold, but still significantly higher compared to normal glomeruli (P ＜0.01). Furthermore, the MGA and MGV in group M were significantly smaller than those of group D (P ＜0.01). Conclusion] Melatonin possesses a renal protective effect on diabetic rats,whose mechanism may be associated partly with a down-regulation of the expression of TGF-β1 mRNA.