雷公藤多苷对糖尿病肾病大鼠肾组织转化生长因子ß1、骨发生蛋白7及Gremlin表达的影响

肾脏病与透析肾移植杂志 ›› 2012, Vol. 21 ›› Issue (3): 237-243.

雷公藤多苷对糖尿病肾病大鼠肾组织转化生长因子ß1、骨发生蛋白7及Gremlin表达的影响

出版日期:2012-06-28 发布日期:2012-06-25

Intervention with Triptergium Wilfordii Polyglucoside on Expression of TGF-β1、BMP-7 and Gremlin in Renal Tissue of Diabetic Nephropathy Rats.

Online:2012-06-28 Published:2012-06-25

摘要/Abstract

摘要：

摘要目的：观察雷公藤多苷（TWP）对糖尿病肾病(DN)大鼠模型肾组织转化生长因子ß1（TGF-ß1）、骨发生蛋白7（BMP-7）、Gremlin的表达干预，阐明TWP延缓肾间质纤维化的机制。方法：将40只雄性SD大鼠随机分为正常对照组，实验组。实验组行高糖高脂饮食+链脲佐菌素腹腔注射建立糖尿病肾病大鼠模型，将造模成功的大鼠随机分为DN组、TWP治疗组。治疗组经口灌胃TWP（50mg/Kg.d）,第2、4、8、16周称鼠重并检查24h尿蛋白排泄量及尿NAG，第16周处死大鼠并抽取血液，摘除肾脏，观察血清生化指标，肾间质纤维化，免疫组化检测肾组织内TGF-ß1、BMP-7、Gremlin的表达，借助RT-PCR和Western blotting方法检测肾组织内TGF-ß1、BMP-7、Gremlin核酸及蛋白的表达。结果：TWP减轻模型鼠蛋白尿，改善血清白蛋白，降低血清肌酐、尿素氮。下调模型鼠肾组织内TGF-ß1、Gremlin的核酸及蛋白表达，上调BMP-7的核酸及蛋白表达。结论：TWP可以延缓肾组织纤维化。机制：可能与TWP抑制促纤维TGF-ß1及下游细胞因子Gremlin的表达，上调抗纤维化因子BMP-7的表达。

关键词: 雷公藤多苷 , 糖尿病肾病 , 肾纤维化 , 转化生长因子ß1 , Gremlin骨发生蛋白7

Abstract:

ABSTRACT Objective：To observing the effect of tripterygium wilfordii polyglucosides on the expression of transforming growth factor-β1 (TGF-β1) 、bone morphogenetic protein (BMP-7) and Gremlin in renal tissue of diabetic nephropathy rats, to explain the mechanism of triptergium wilfordii polyglucoside delay renal interstitial fibrosis. Methodology： Forty Sprague – Dawlay (SD) rats were randomly divided into normal control group, diabetes mellitus control group (group DN) and triptergium wilfordii polyglucoside treated diabetes mellitus group (group TWP). Diabetes mellitus were induced by high sugar and fat diet and streptozocin(STZ), and groupTWP were treated with triptergium wilfordii polyglucoside（50mg/Kg•d）. The weight of rat、24 hours protein (24 h U - TP) and urine NAG were examined in 2th 、4th、8th and 16th week. After 16 weeks, blood glucose(GLU) , serum creatinine (Scr ), blood urea nitrogen(BUN), kidney hypertrohy index were measured. Partial nephridial tissue were observed HE staining. Mean glomerular area and mean glomerular volume were determined. RT-PCR，western blotting，immunohistochemistry were used to analyse TGF-β1 、BMP-7 and Gremlin gene and protein expression in kidney tissue of three group rats. Results：Compared with the untreated diabetic group, urinary albumin excretion, serum creatinine and blood urea nitrogen of triptergium wilfordii polyglucoside treated rats were substanitially decreased. The expression of TGF-ß1 and Gremlin were lower and BMP-7 were upper in triptergium wilfordii polyglucoside treated group. Conclusions：Triptergium wilfordii polyglucoside has protective effect on renal interstitial fibrosis in diabetic rats, partly through down-regulating TGF-ß1、Gremlin and up-regulating BMP-7.

Key words: triptergium wilfordii polyglucoside , diabetic nephropathy , renal interstitial fibrosis , TGF-ß1 , Gremlin , BMP-7

张燕，常保超，陈卫东. 雷公藤多苷对糖尿病肾病大鼠肾组织转化生长因子ß1、骨发生蛋白7及Gremlin表达的影响[J]. 肾脏病与透析肾移植杂志, 2012, 21(3): 237-243.

ZHANG Yan，CHANG Bao-shao，CHEN Wei-dong . Intervention with Triptergium Wilfordii Polyglucoside on Expression of TGF-β1、BMP-7 and Gremlin in Renal Tissue of Diabetic Nephropathy Rats.[J]. Chinese Journal of Nephrology, Dialysis & Transplantation, 2012, 21(3): 237-243.

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