【摘要】 目的探讨微管相关蛋白1轻链3(LC3)在早期糖尿病大鼠肾脏中表达的意义及其与糖尿病肾病(DN)发生发展的关系。方法实验分为模型组和正常对照组。采用链脲佐菌素(STZ)诱导大鼠DN模型,分别于造模成功后2、4、6、8周,用免疫组化、原位末端标记法(TUNEL)染色分析和计算机图像分析技术连续多时点观察肾脏LC3的表达变化和细胞凋亡情况,并分析二者之间的关系及其与肾脏病理变化指标的相关性。结果模型组2、4、6、8周肾脏LC3蛋白表达均弱于对照组(P<0.05);模型组各时点间LC3表达水平比较,差异有统计学意义(P<0.01)。模型组LC3的表达量与尿蛋白、肾脏肥大指数(KI)呈负相关(P<0.01)。模型组2、4、6、8周肾小管细胞凋亡细胞增均高于对照组(P<0.05);模型组各时间点肾小管细胞凋亡指数比较,差异均有统计学意义(P<0.01)。模型组肾脏细胞凋亡指数与尿蛋白、KI呈正相关(P<0.01)。LC3表达量与细胞凋亡指数呈负相关(P<0.01)。结论自噬的缺乏可能促进了DN的发展,细胞凋亡参与了早期DN的发生发展,两者相互作用,可能加重糖尿病的肾脏损伤。更多还原

【Abstract】 Objective To explore the significance of LC3 expression in the renal tissue of early-stage diabetic rats and relationship between LC3 expression and development of diabetic nephropathy.Methods The Sprague-Dalwley(SD) rats were divided into the diabetic and control groups.The diabetic group was treated by streptozotocin(STZ).The expression of LC3 in renal tissue was detected by immunohistochemistry and the apoptosis of renal cell was measured by TUNEL assay at 2,4,6 and 8weeks.The level of LC3 expression and the apoptotic index(AI) of renal cell were quantified by computer image analysis.The relationship between LC3 expression and the renal AI,kidney/body weight(KI),urinary protein excretion was analyzed.Results As compared with the control group,LC3 expression in kidney tubules of the diabetic group was significantly decreased at the same time points of 2,4,6 and 8 weeks(P<0.05).The level of LC3 expression was negatively correlated with kidney/body weight and urine protein excretion(P<0.01).The renal tubular cells AI was higher than that of control group(P<0.05) and positively correlated with kidney/body weight and urine protein excretion(P<0.01),respectively.It was found that there was a strong negative correlation between the level of LC3 expression and the renal cell AI(P<0.01).Conclusion The downregulated expression of LC3 and the increased apoptosis of renal cells in early stage DN rats may contribute to the development of DN.Their interaction may promote the renal injury of diabetes mellitus.更多还原