去乙酰化蛋白酶1在马兜铃酸肾纤维化模型中对TGF-β1/Smad7信号通路的作用  

The Role of HDAC1 in the Signal Pathway of TGF-β1/Smad7 in AAN Model

作　　者：杨洋[1,2] 张中文[2] 姚华[2] 高磊[2] 李培锋[1] 吴国娟[2] 

机构地区：[1]内蒙古农业大学兽医学院,呼和浩特010018 [2]北京农学院动物科学技术学院,北京102206

出　　处：《畜牧兽医学报》2012年第3期459-468,共10页ACTA VETERINARIA ET ZOOTECHNICA SINICA

基　　金：国家自然科学基金资助项目(31172362;30972215);北京市属高校人才强教计划资助项目(PHR);北京市自然科学基金资助(6092004;5102014);北京市教委项目资助(KM 201010020008)

摘　　要：检测马兜铃酸肾纤维化(AAN)模型肾组织中转化生长因子-β1(TGF-β1)、Smad7、去乙酰化蛋白酶1(HDAC1)的mRNA和蛋白表达变化,探讨HADC1和Smad7的表达在AAN发展中的作用及两者间的联系。RT-PCR检测TGF-β1、Smad7和HDAC1的mRNA表达,ELASA检测TGF-β1的蛋白表达,免疫组化定位和检测HADC1和Smad7蛋白,HE染色观察肾病理学改变。结果显示:AAN模型肾组织中TGF-β1和HDAC1mRNA表达呈时间依赖性升高,TGF-β1mRNA表达较对照组有明显差异(P<0.05),28d开始AAN组中HDAC1mRNA增加,差异极显著(P<0.01);Smad7mRNA和蛋白表达均呈下降趋势,HDAC1蛋白免疫组化染色强度呈上调趋势,与对照组比较HDAC1阳性着色主要分布于上皮细胞和间质细胞的细胞核;肾脏病理表现为肾小管浊肿、变性和脱落等急性小管间质损伤,并随用药时间的延长呈进行性加重。本研究表明肾组织中Smad7弱表达可促进TGF-β1信号转导,HDACl mRNA和蛋白在肾组织中的高表达并参与TGF-β1/Smad7信号通路在肾纤维化发展中起重要作用,可能是潜在的新作用靶点。The aim of this study was to study the changes in the expression of transforming growth factor β1 （TGF-β1）, the TGF-131 receptor （TβR-I）, SmadT, and histone deacetylase 1 （HDAC1） in mice with aristolochic acid nephropathy （AAN）, and analyze the relationship be- tween HDAC1 and SmadT. RT-PCR was applied to detect the mRNA levels of TGF-β1, Smad7 and HDAC1 in kidneys. The TGF-β1 concentrations were determined by ELISA. HADC1 and Smad7 proteins were localized and detected by immunohistochemistry method. The tissue section technique was used to observe the histopathologic changes, such as kidney damage and renal tu- bules interstitial fibrosis degree. Results were as follows： In mice with induced AAN, the mRNA levels for TGF-β1 and HDAC1 were increased with treatment time. The mRNA levels for TGF-β1were higher than that of their control （normal mice without treatment） （P〈0.05）. Starting from 28 day, mRNA of HDAC1 became significantly higher than the level of the control （P〈0.01）. The levels of Smad7 protein and its mRNA were decreased with time, and lower than that of con-trol. HDAC1 protein expression was increased with time post treatment. Compared with the con trol group, HDAC1 positive stains were mainly distributed in the epithelial and stromal cell nu- cleus. Histopathologic changes of kidney showed acute tubular interstitial damage, such as tur- bidity, swollen, degeneration and fall off of renal tubular. With extension of treatment time, re- nal tubular damage was aggravated progressively. During the development of AAN in mice, Smad7 can cause renal tubular damage, impare renal tubular renewable repair ability, restrain Smad7 mRNA expression. The weak expression of Smad7 in renal tissues can promote TGF-~I signal transduction, help the fibre formation and maintain the proliferation condition. One of the mechanism happened is about HDAC1, which mRNA and protein high expressions plays an im- portant role in the development aristolochinc acid nephropathy, may be a new pot

关 键 词：AAN TGF-Β1 SMAD7 HDAC1 

分 类 号：S852.3[农业科学—基础兽医学]