糖尿病大鼠肾脏nephrin表达的动态观察

Expression of nephrin in rats with diabetic nephropathy

目的从不同时间点动态观察足细胞相关分子nephrin在糖尿病大鼠肾组织中的表达,探讨nephrin在DN蛋白尿发生发展中的改变及意义。方法将SD大鼠分为健康对照组(C组)、糖尿病组(DM组)。SD大鼠腹腔注射链脲佐菌素制成糖尿病模型,正常对照组注射等量枸橼酸缓冲液。分别于0、2、4、6、8、12周动态检测尿白蛋白(UA),血糖(BG)及肾功能,取肾组织行常规病理检查,免疫组化、Western blot分析技术检测肾脏nephrin的表达。结果 (1)与NC组相比,DM组随着病程的延长,尿白蛋白、BUN、Ccr均逐渐出现明显的变化,而白蛋白尿早于BUN、Ccr异常的出现;(2)与NC组相比,DM组足细胞相关分子nephrin蛋白于第2周出现表达下调,随着时间的进展,nephrin蛋白的表达进一步减少,直至第12周,各周间比较差异有显著性(P<0.05);(3)相关分析显示:尿白蛋白排泄与足细胞相关分子nephrin呈负相关。结论糖尿病大鼠早期(2周)出现足细胞相关分子nephrin表达下调,是糖尿病肾病早期损伤指标,nephrin参与了糖尿病肾病大鼠蛋白尿的发生及发展。

Purpose To observe the expression of nephrin in the kidney of diabetic rats dynamically at the different stages,and to investigate the changes and significance of nephrin in the lesion.Methods The SD rats were divided into control group,and diabetic group（DM group）.SD rats were intraperitoneally injected with streptozotocin by which diabetes model was made.The normal control group rats were injected with equivalent citrate buffer.Urinary albumin（UA）,blood glucose（BG） and renal function were detected dynamically at 0,2,4,6,8,and 12 weeks,and renal tissue were also analyzed by conventional pathological examination.The protein expression of nephrin was detected by immunohistochemistry,and Western blot analysis.Results Compared with the control group,with the extension of the course of the disease,urinary albumin,BUN and Ccr in the DM group were gradually changed significantly,but albuminuria appeared earlier than abnormalities of BUN and Ccr;the expression of podocyte-associated molecules nephrin was decreased in DM group at 2th week.With time,nephrin expression was decreased further until 12 weeks,and the difference was significant between every weeks（P0.05）;the excretion of urinary albumin was showed negative correlation with podocyte-associated molecules nephrin showed by correlation analysis.Conclusions Nephrin expression is decreased at early time in diabetic rats,which is an indicator of early damage in diabetic nephropathy.Nephrin plays a role in the pathogenesis and development of proteinuria in diabetic nephropathy.