肾苏Ⅱ号方对局灶节段性肾小球硬化大鼠TGF-β<sub>1</sub>及PAI-1表达的影响

Effects of Shensu Ⅱ Recipe on the Expressions of Transforming Growth Factor-β₁ and Plasminogen Activator Inhibitor-1 in the Focal Segmental Glomerulosclerosis Rats

免费下载全文查看/发表评论下载PDF阅读器

DOI：

中文关键词: 局灶节段性肾小球硬化肾苏Ⅱ号方转化生长因子-β1 纤溶酶原激活物抑制物-1

英文关键词:focal segmental glomerulosclerosis Shensu Ⅱ Recipe transforming growth factor β1 plasminogen activator inhibitor-1

基金项目:国家自然科学基金资助项目(No.30772808)

作者	单位
杨洪涛	天津中医药大学第一附属医院肾病科
窦一田	天津中医药大学研究生院
曹式丽	天津中医药大学第一附属医院肾病科

摘要点击次数: 1406

全文下载次数: 1

中文摘要:

目的观察中药复方肾苏Ⅱ号方对局灶节段性肾小球硬化(FSGS)大鼠肾功能、肾小球细胞外基质(ECM)积聚、转化生长因子-β1(TGF-β1)及纤溶酶原激活物抑制物-1(PAI-1)表达的影响。方法阿霉素注射法诱发SD大鼠FSGS型阿霉素肾病模型,依体重随机分为模型组、西药组及中药组,每组各12只,另设空白对照组(对照组,12只)。西药组予灌胃贝那普利(0.33mg/100g),中药组予肾苏Ⅱ号方(3.5g/100g)灌胃,对照组和模型组予等量生理盐水灌胃。实验过程中死亡6只大鼠,其中,对照组1只,模型组2只,西药组1只,中药组2只。检测24h尿蛋白定量(24hU,邻苯三酚红法)、血尿素氮(BUN,尿素酶法)、血肌酐(SCr,肌酐酶法)、血清总蛋白(TP,双缩脲比色终点法)、血清白蛋白(ALB,溴甲酚绿比色测定法);观察肾小球病理形态学改变;半定量分析肾小球纤维连接蛋白(FN)、Ⅳ型胶原(ColⅣ)全肾平均硬化指数(GSI)、ECM与肾小球面积比(ECM/GA)及TGF-β1、PAI-1表达。结果治疗第12周末,中药组FSGS大鼠生化指标24hU[(38.55±2.49)mg]、BUN[(10.87±1.78)mmol/L]、SCr[(51.70±1.50)μmol/L]、TP[(68.28±2.31)g/L]、ALB[(42.43±1.95)g/L]改善;病理形态学观察肾小球硬化进展显著延缓;半定量分析GSI[(1.68±0.33)级]、ECM/GA[(7.11±2.46)%]、FN[(4.15±1.55)%]、ColⅣ[(1.47±0.48)%]、TGF-β1[(19.70±5.05)%]、PAI-1[(22.57±10.65)%],与模型组比较,差异有统计学意义(P<0.05,P<0.01)。结论肾苏Ⅱ号方可能通过抑制TGF-β1、PAI-1表达,阻抑基质过度积聚,进而延缓FSGS大鼠肾小球硬化进展。

英文摘要:

Objective To observe the effects of Shensu Ⅱ Recipe on the renal function,mesangial extracellular matrix(ECM) accumulation,the expressions of transforming growth factor-β1(TGF-β1) ,and plasminogen activator inhibitor-1(PAI-1) in the focal segmental glomerulosclerosis(FSGS) rats. Methods FSGS SD rat model was induced by injecting adriamycin. They were randomly divided into the model group,the Western medicine group,and the Chinese medicine group according to body weight. Besides,another 12 rats was taken as the blank control group. Of them,benazepril(0.33 mg/100 g) was given to rats in the Western medicine group by gastrogavage,while Shensu Ⅱ Recipe(3.5 g/100 g) was given to rats in the Chinese medicine group by gastrogavage. Normal saline was given to rats in the control group and the model group by gastrogavage. Six rats died during the experiment process,among which,one in the control group,two in the model group,one in the Western medicine group,and two in the Chinese medicine group. The changes of 24 h urinary protein(24 hU,pyrogallol red method) ,blood urea nitrogen(BUN,urease method) ,serum creatinine(SCr,enzymatic assay of creatinine) ,serum total protein(TP,biuret colorimetry) ,serum albumin(ALB,bromocresol green colormetry) were detected. The pathomorphological changes of the glomerulus were observed. Fibronection(FN) ,collagen Ⅳ(Col Ⅳ) ,glomerulus sclerosis index(GSI) ,ECM/glomerulus area(GA) ,expressions of TGF-β1 and PAI-1 were determined by semi-quantitative analysis. Results At the end of the 12th week,improvement was shown in the Chinese medicine group(24 hU:38.55±2.49 mg;BUN:10.87±1.78 mmol/L;SCr:51.70±1.50 μmol/L;TP:68.28±2.31 g/L;and ALB:42.43±1.95 g/L) . The pathomorphological observation showed that the development of glomerulosclerosis(GS) was significantly slowed down. Semi-quantitative analysis showed significant difference when compared with the model group(GSI:1.68±0.33 grade;ECM/GA:7.11%±2.46%;FN:4.15%±1.55%;Col Ⅳ:1.47%±0.48%;TGF-β1:19.70%±5.05%;PAI-1:22.57%±10.65%) (P<0.05,P<0.01) . Conclusion Shensu Ⅱ Recipe could postpone the development of GS in FSGS rats possibly through inhibiting the expressions of TGF-β1 and PAI-1,hindering the over-accumulation of mesangial matrix.

关闭