丹参酮Ⅱ_A对阿霉素肾病大鼠肾小球nephrin和TGF-β_1的表达影响  

Effects of Tanshinone Ⅱ_A on Renal Nephrin and Transforming Growth Factor-β_1 of Adriamycin Nephritic Rats

作　　者：王军建[1] 胡锐 

机构地区：[1]西安市儿童医院急诊科,西安710002 [2]陕西省交通医院儿科,西安710068

出　　处：《中国实验方剂学杂志》2011年第19期245-251,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：陕西省科技攻关项目(2002K11-G8)

摘　　要：目的:探讨肾小球足细胞跨膜蛋白(nephrin)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)在阿霉素肾病大鼠肾小球中的表达变化及丹参酮ⅡA对其影响。方法:SD大鼠56只随机分为2组,模型组44只和对照组12只。模型组大鼠尾静脉一次注射盐酸阿霉素(ADR)0.007 g.kg-1,对照组大鼠尾静脉注射等容积生理盐水,注射ADR 1周后尿蛋白定量>100 mg.(24 h)-1即算建模成功,共有40只大鼠建模成功,随机又分为肾病模型组、泼尼松组、丹参酮ⅡA低剂量组和高剂量组,每组10只。泼尼松组给予泼尼松0.01 g.kg-1.d-1 ig;丹参酮ⅡA低剂量组和高剂量组分别给予丹参酮ⅡA 0.02,0.04 g.kg-1.d-1 ig,共4周。对照组和肾病模型组给予等容积生理盐水ig。实验结束后检测各组大鼠血、尿生化指标,光镜观察肾脏病理学改变,免疫组化技术和Western blotting技术检测nephrin和TGF-β1的表达。结果:肾病模型组、泼尼松组、丹参酮ⅡA低剂量组和高剂量组24 h尿蛋白定量、胆固醇、甘油三酯、血尿素氮、血肌酐和肾小球TGF-β1表达均高于对照组(P<0.05),但泼尼松组和丹参酮ⅡA高剂量组上述指标均低于肾病模型组(P<0.05);肾病模型组、泼尼松组、丹参酮ⅡA低剂量组和高剂量组血清总蛋白、白蛋白、肾小球nephrin表达低于对照组(P<0.05),但泼尼松组和丹参酮IIA高剂量组血清总蛋白、白蛋白、nephrin表达高于肾病模型组(P<0.05)。结论:Nephrin及TGF-β1在阿霉素肾病发病机制中起重要作用;丹参酮ⅡA能够增加肾组织nephrin的表达,抑制TGF-β1的表达,减少阿霉素肾病大鼠尿蛋白的排出,减轻及延缓肾小球硬化,发挥保护肾脏的作用。Objective：To explore effects of tanshinone ⅡA on expression changes of nephrin and transforming growth factor-β1（TGF-β1）in adriamycin（ADR）-induced-nephropathy rats.Method： Fifty-six rats of Sprague-Dawley were divided into two groups：the model group（n=44）and the control group（n=12）.The rats in the model group were injected with a single dose of ADR（0.007 g·kg-1）via tail-vein,while the rats in the control group were injected with a comparable volume of 0.9% saline.The model was successfully established when the 24 h urinary protein excretion exceeded 100 mg after ADR injection 1 week,forty rats were successful and then were randomly assigned to the ADR nephrosis group（n=10）,prednisone group（n=10）,the low dose and high dose of tanshinone ⅡA group（n=10）.The rats in the prednisone group were treated with prednisone（0.01 g·kg-1·d-1）,ig,The rats in the low dose and high dose of tanshinone ⅡA group were treated with tanshinone ⅡA（0.02 g·kg-1·d-1 or 0.04 g·kg-1·d-1）,ig,once a day for 4 weeks,whereas the other rats were received a comparable volume of 0.9% saline.The blood and urina biochemical indicators were measured and the pathological changes of the renal tissues were observed under light microscope,immunohistochemical and Western blotting techniques to detect the expression of nephrin and TGF-β1.Result： The 24 h urinary protein,cholesterol,triglyceride,blood urea nitrogen,serum creatinine,and the expression of TGF-β1 in the ADR nephrosis group,prednisone group,the low dose and high dose of tanshinone ⅡA group were higher than those in the control group（P0.05）.The total protein,albumin and the expression of nephrin in the ADR nephrosis group,prednisone group,the low dose and high dose of tanshinone ⅡA group was lower than those in the control group（P0.05）.After treatment with prednisone and the high dose of tanshinone ⅡA could improve above-mentioned indicators.Conclusion：Nephrin and TGF-β1 play an important role in the pathogenesis o

关 键 词：阿霉素肾病 蛋白尿 NEPHRIN 转化生长因子-Β1 丹参酮ⅡA 

分 类 号：R365.69[医药卫生—病理学] R285[医药卫生—基础医学]