骨桥蛋白与糖尿病大鼠肾小管病变的关系探讨

The relationship between osteopontin and tubular injury in diabetes rats

目的研究骨桥蛋白在糖尿病(DM)大鼠肾小管病变中的作用。方法将35只大鼠随机分为健对照组及DM模型组(4组);动态观察血糖、肾功能、24 h尿白蛋白排泄率(UAER)、尿α1-MG的变化;免疫组化检测肾脏骨桥蛋白(OPN)及ED-1的表达;分析OPN表达与肾小管损伤标志物的关系。结果与对照组相比,模型组大鼠随病程进展,肾功能、尿UAER、尿α1-MG的水平逐渐上升(P<0.01);模型组肾脏中OPN表达及ED-1数目随DN病程进展而显著增多(P<0.01)。肾脏中OPN表达上调先于巨噬细胞浸润的增多,巨噬细胞主要聚集于表达OPN的肾小管区域;OPN的表达强度与巨噬细胞浸润数目呈正相关(P<0.01),与小管损伤的标志物α1-MG水平亦呈正相关(P<0.01)。结论OPN于DN肾小管病变早期即出现表达上调,可能通过诱导巨噬细胞浸润,参与DN的小管病变。

Objective To investigate the significance of osteopontin （OPN） in tubular injury of STZ- induced diabetes wistar rats. Methods Thirty-five Wistar rats＇ were randomly divided into the normal control group （ group A） and DM models groups （ groups B, C, D, and E）. The changes of glycemia, renal functional, urinary albumin excretion rate （UAER）, and urinary α1-Microglobulin （α1-MG） were evaluated periodically and the expressions of OPN and ED-1 were detected by using immunohistochemistry method. The relationship between the expression of OPN and the tubular injury was analyzed. Results The levels of UAER and urinary α1-MG,and the renal function were improved in the rats of DM models groups （ P 〈0. 01 ）. The expressions of OPN and ED-1 were up-regulated in the DM rats （ P 〈0. 01 ）. The macrophages were localized in the region of renal tubule in which the OPN was expressed. The expression of OPN was significantly correlated with the number of ED-1-positive cells and the level of urinary α1-MG（ P 〈 0. 01 ）. Conclusion The up - regulation of OPN may induce macrophage infiltration and may be involved in the tubular injury associated with diabetic nephropathy.