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[骨形态发生蛋白7对糖尿病大鼠肾脏中nephrin表达及分布的影响]

[Effect of bone morphogenic protein 7 on nephrin expression and distribution in diabetic rat kidneys].

作者信息

Xiao Hou-qin, Shi Wei, Zhang Yong, Liang Yong-zheng

机构信息

Department of Nephrology, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou 510080, China. xhq7301 @tom.com

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2009 Apr;29(4):671-5.

Abstract

OBJECTIVE

To evaluate the effect of bone morphogenic protein 7 (BMP-7) on nephrin expression and distribution in diabetic rat kidneys.

METHODS

Twenty rats with diabetes mellitus (DM) induced by streptozotocin (STZ) injection were randomly divided into DM model group and BMP-7 treatment group, with another 10 normal rats serving as the normal control group. The rats in BMP-7 group received intraperitoneal human recombinant BMP-7 injections at 30 microg/kg twice a week for 24 consecutive weeks, while normal saline was administered in rats of the other two groups. Blood glucose and 24 hour urinary protein and creatinine (Ccr) were measured at 8, 16 and 24 weeks, and the rats were sacrificed at 24 weeks to obtain the renal tissues for detecting the expression and distribution of nephrin using immunofluorescence assay and RT-PCR and for examining the expressions of transforming growth factor-beta1 (TGF-beta1) and WT1 using immunohistochemistry.

RESULTS

Compared with the normal control group, the DM model group showed significantly increased 24 hour urinary protein, kidney to body weight ratio and TGF-beta1 expression, but had lowered Ccr, glomerular podocyte number and nephrin expression. The linear distribution of nephrin along the capillary loops as found in the normal control group became granular in the kidney of diabetic rats. The rats in BMP-7 group showed less urinary protein excretion, lower TGF-beta1 expression and greater glomerular podocyte number than those in the DM group, and the expression and distribution of nephrin remained normal in the kidney.

CONCLUSION

Administration of BMP-7 can significantly suppress the down-regulation of nephrin expression and maintain its normal distribution in the podocytes in diabetic rats possibly in association with a direct suppression of TGF-betasignaling.

摘要

目的

评估骨形态发生蛋白7(BMP - 7)对糖尿病大鼠肾脏中nephrin表达及分布的影响。

方法

将20只经链脲佐菌素(STZ)注射诱导的糖尿病(DM)大鼠随机分为DM模型组和BMP - 7治疗组,另10只正常大鼠作为正常对照组。BMP - 7组大鼠每周两次腹腔注射人重组BMP - 7,剂量为30μg/kg,连续24周,而另外两组大鼠给予生理盐水。在第8、16和24周测量血糖、24小时尿蛋白和肌酐清除率(Ccr),并在第24周处死大鼠以获取肾组织,采用免疫荧光法和RT - PCR检测nephrin的表达及分布,采用免疫组化法检测转化生长因子 - β1(TGF - β1)和WT1的表达。

结果

与正常对照组相比,DM模型组24小时尿蛋白、肾重与体重比及TGF - β1表达显著增加,但Ccr、肾小球足细胞数量和nephrin表达降低。正常对照组中沿毛细血管袢呈线性分布的nephrin在糖尿病大鼠肾脏中变为颗粒状。BMP - 7组大鼠的尿蛋白排泄量低于DM组,TGF - β1表达较低,肾小球足细胞数量较多,且肾脏中nephrin的表达及分布保持正常。

结论

给予BMP - 7可显著抑制糖尿病大鼠中nephrin表达的下调,并维持其在足细胞中的正常分布,这可能与直接抑制TGF - β信号有关。

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