骨桥蛋白在糖尿病大鼠肾组织中的表达及意义

目的 观察糖尿病大鼠肾组织中骨桥蛋白(OPN)的表达及其与巨噬细胞(CD68)、细胞增殖核抗原(PCNA)之间的关系,初步探讨其在糖尿病肾损害中的意义.方法 雄性Wistar大鼠被随机均分为对照组和糖尿病组,每组24只.腹腔单次注射链脲佐菌素(STZ)诱发糖尿病大鼠模型,采用免疫组化和蛋白质免疫印迹法(Western blotting)分别检测OPN、CD68及PCNA在肾组织的表达,原位杂交检测肾组织中OPN mRNA的表达.结果 与对照组比较,糖尿病组大鼠在注射STZ后1、2、4和8周,血糖、尿素氮(BUN)和24 h尿蛋白定量显著增高,肌酐清除率(CCr)显著降低;OPN表达呈进行性增加并明显高于对照组(P均＜0.05);1周和2周时PCNA表达高于对照组,4周和8周时CD68表达较对照组略有增高.结论 OPN在糖尿病肾损害过程的早期可能与肾小管上皮细胞增殖有关,后期可能趋化巨噬细胞浸润.

Expression and implication of osteopontin in renal cortex of diabetic rats

OBJECTIVE: To investigate the expression and implication of osteopontin (OPN) in renal cortex of diabetic rats. METHODS: Experimental diabetes was reproduced in uninephrectomized rats by giving streptozotocin (STZ). The animals were divided into two groups: control group and diabetic group (each n=24). Immunohistochemistry and Western blotting were used to detect the protein expression of OPN, CD68, and proliferating cell nuclear antigen (PCNA). At the same time the mRNA expression of OPN was detected by in situ hybridization. RESULTS: Compared with control group, blood glucose, blood urea nitrogen (BUN), 24-hour urine protein quantum and quantification of OPN protein significantly increased while creatinine clearance rate (CCr) was significantly decreased in diabetic rat group 1, 2, 4 and 8 weeks after STZ injection. The protein of PCNA were also higher than that of control group 1 and 2 weeks after STZ injection (all P<0.05), and the increase in CD68 was observed at week 4 and week 8. CONCLUSION: Overexpression of OPN may be responsible for the proliferation of tubular cells at early stage of diabetic nephropathy and for the accumulation of macrophage at later stage.