雷公藤多苷对糖尿病肾病大鼠肾组织转化生长因子β1、骨形成蛋白7及Gremlin表达的影响  

Triptergium wilfordii polyglucoside interfere the expression of TGF-β1、BMP-7 and Gremlin in renal tissue of diabetic nephropathy rats

作　　者：张燕[1] 常保超[1] 陈卫东 

机构地区：[1]蚌埠市蚌埠医学院第一附属医院肾脏科蚌埠,233004

出　　处：《肾脏病与透析肾移植杂志》2012年第3期237-243,共7页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：目的:观察雷公藤多苷(TW)对糖尿病肾病(DN)大鼠模型肾组织转化生长因子β1(TGF-β1)、骨形成蛋白7(BMP-7)、Gremlin表达的干预,阐明TW延缓肾间质纤维化的机制。方法:40只雄性SD大鼠随机分为实验组及对照组。实验组行高糖高脂饮食,并以链脲佐菌素腹腔注射建立DN大鼠模型,将造模成功的大鼠随机分为DN组和TW治疗组。治疗组经口灌胃TW(50mg/Kg·d),第2、4、8、16周称鼠重并查24h尿蛋白定量及尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG),第16周处死大鼠抽取血液,观察血清生化指标,摘除肾脏行组织切片,观察肾间质纤维化程度,免疫组化检测肾组织内TGF-β1、BMP-7、Gremlin的表达,借助RT-PCR和Westernblotting方法检测肾组织内TGF-β1、BMP-7、Gremlin核酸及蛋白的表达。结果:TW能减轻模型鼠蛋白尿,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-β1、Gremlin的核酸及蛋白表达,上调BMP-7的核酸及蛋白表达。结论:TW可延缓肾组织纤维化,其机制可能与TW抑制促纤维化TGF-β1及下游细胞因子Gremlin的表达,上调抗纤维化因子BMP-7的表达相关。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（50 mg/Kg.d）. The weight of rat,24 hours protein （24h 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 glomernlar 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-i31 and Gremlin were lower and BMP-7 were upper in triptergium wilfordii polyglucoside treated group. Conclusion：Triptergium wilfordii polyglucoside has protective effect on renal interstitial fibrosis in diabetic rats ,partly through down-regulating TGF-β1 ,Gremlin and up-regulating BMP-7.

关 键 词：雷公藤多苷 糖尿病肾病 肾纤维化 转化生长因子β1 GREMLIN 骨形成蛋白7 

分 类 号：R285.5[医药卫生—中药学]