虫草菌粉对慢性马兜铃酸肾病大鼠肾组织TGF-β<sub>1</sub>及Snail表达和TEMT的影响

Effects of Hirsutella Sinensis on TGF-β₁ and Snail Expressions and Transdifferentiation of Tubular Epithelial-myofibroblast in Renal Tissue of Rats with Chronic Aristolochic Acid Nephropathy

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DOI：

中文关键词: 马兜铃酸虫草菌粉转化生长因子-β₁ 肾小管上皮-肌成纤维细胞转分化间质纤维化

英文关键词:aristolochic acid Hirsutella sinensis Powder transforming growth factor-β1 renal tubular epithelial-myofibroblast transdifferentiation interstitial fibrosis

基金项目:卫生部属(管)医疗机构临床学科重点项目(2005-2007年度)

作者	单位
柴晶晶	卫生部中日友好医院肾病中心郑州大学第一附属医院肾病风湿科
谌贻璞	卫生部中日友好医院肾病中心
芮宏亮	卫生部中日友好医院肾病中心
董鸿瑞	卫生部中日友好医院肾病中心
刘章锁	郑州大学第一附属医院肾病风湿科

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中文摘要:

目的研究虫草菌粉对慢性马兜铃酸肾病(CAAN)模型大鼠肾小管上皮-肌成纤维细胞转分化(TEMT)的拮抗作用。方法雄性SD大鼠随机分为对照组、模型组、虫草组,每组6只。检测0、1、4、8、12周各组大鼠24h尿蛋白定量及0、12周肌酐清除率(CCr);第12周末处死大鼠留取肾组织,行Masson染色观察肾间质纤维化程度;并用逆转录实时聚合酶链反应和免疫组织化学方法检测肾组织中转化生长因子-β1(TGF-β1)、Snail、α-平滑肌肌动蛋白(α-SMA)及角蛋白的mRNA及蛋白质表达。结果与对照组比较,模型组大鼠CCr显著下降(P<0.01),24h尿蛋白定量显著增高(P<0.01);肾间质纤维化面积显著扩大(P<0.01);肾组织内TGF-β1、Snail及α-SMA的mRNA和蛋白质水平显著上调(P<0.05或P<0.01);角蛋白的mRNA和蛋白质水平显著下降(P<0.01)。与模型组比较,虫草组大鼠CCr显著增高(P<0.05),24h尿蛋白定量及肾间质纤维化面积显著减少(P<0.05);上述高表达的mRNA及蛋白质指标均被显著抑制(P<0.05),角蛋白的mRNA和蛋白质表达显著上升(P<0.05)。结论虫草菌粉能下调CAAN大鼠肾组织TGF-β1及Snail表达,拮抗TEMT及肾间质纤维化,改善肾功能。

英文摘要:

Objective To investigate the antagonizing effect of Hirsutella sinensis(HS) on renal tubular epithelial-myofibroblast transdifferentiation(TEMT) and its possible pathogenic mechanism in rats with chronic aristolochic acid nephropathy(CAAN).Methods Eighteen male Sprague-Dawley rats were equally divided into 3 groups,the model(M) group,the intervention(I) group and the control(C) group.The 24 h urinary protein(UP) in rats was measured before intervention and at the end of the 1st,4th,8th,and 12th week,and creatinine clearance rate(CCr) was measured before intervention and at the end of the 12th week respectively.All rats were sacrificed at the end of the 12th week,their kidney was taken for examining the degree of fibrosis in renal interstitial with Masson’s stain and determining mRNA and protein expressions of transforming growth factor-β1(TGF-β1),Snail,α-smooth muscle actin(α-SMA) and cytokeratin in renal tissue by Real-time RT-PCR and immunohistochemistry staining,respectively.ResultsCompared with the C group,CCr was significantly lower,while 24 h UP was higher;the relative area of interstitial fibrosis was significantly larger in the M group;besides,the mRNA and protein expressions of TGF-β1,Snail and α-SMA were significantly up-regulated(P<0.01 or P<0.05),and those of cytokeratin were significantly down-regulated(P<0.01) in renal tissue of the M group.While in the I group,all the above-mentioned abnormalities were restored to some extent(P<0.05) and showed significant difference(all P<0.05) as compared with those in the M group.Conclusion HS can down-regulate TGF-β1 and Snail expressions in renal tissue,antagonize TEMT and renal interstitial fibrosis,and improve renal function in CAAN rats.

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