天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (7): 810-813.doi: 10.11958/20150242

• 专题研究·胆道闭锁与肝移植 • 上一篇    下一篇

TGF-β1、 Smad2在胆道闭锁肝纤维化中的作用

丁美云 ， 詹江华 ， 赵丽 ， 赵林胜 ， 张爱华   

  1. 1 天津医科大学研究生院（邮编 300070）；2天津市儿童医院
  • 收稿日期:2015-10-20 修回日期:2016-01-09 出版日期:2016-07-15 发布日期:2016-07-15
  • 通讯作者: 詹江华 E-mail:zhanjianghuatj@163.com
  • 作者简介:丁美云（1988）， 女， 硕士在读， 主要从事小儿普通外科、胆道闭锁方面研究
  • 基金资助:
    国家自然科学基金资助项目（81570471）； 天津市卫生行业重点攻关项目（14KG129）； 天津市卫生局科技基金资助项目（2014KR09）

The function of TGF -β1 and Smad2 in liver fibrosis of Biliary atresia

DING Meiyun, ZHAN Jianghua, ZHAO Li, ZHAO Linsheng, ZHANG Aihua   

  1. 1 The Graduate School of Tianjin Medical University, Tianjin 300070, China; 2 Tianjin Children’ s Hospital
  • Received:2015-10-20 Revised:2016-01-09 Published:2016-07-15 Online:2016-07-15
  • Contact: zhanjianghua E-mail:zhanjianghuatj@163.com

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摘要： 目的 研究转化生长因子（TGF）-β1与Smad2蛋白在胆道闭锁（BA）肝组织中表达情况及在肝纤维化进程中的作用。方法 选取2010年1月—2014年7月尸检（患儿死于非肝胆疾病，正常对照组）5例，胆管扩张症肝活检（胆扩组）10例，BA肝活检（早期肝纤维化组）19例，BA晚期进行肝移植患者自体肝活检（晚期肝硬化组）11例，采用HE染色观察肝标本纤维化评价其纤维化程度，免疫组化染色检测TGF-β1与Smad2蛋白在肝组织中的表达，实时荧光定量聚合酶链式反应（qRT-PCR）方法检测肝组织中TGF-β1与Smad2基因表达情况。结果 HE：正常对照组肝组织无胶原纤维增生，胆扩组有轻度纤维细胞增生，早期肝纤维化组胶原纤维增生、桥接纤维化现象显著，而晚期肝纤维化组假小叶显著。免疫组化：TGF-β1蛋白平均光密度值在早期肝纤维化组表达最高（P<0.05）；Smad2蛋白在4组间表达差异无统计学意义。qRT-PCR：胆扩组、早期肝纤维化组和晚期肝纤维化组三组肝内TGF-β1、Smad2 mRNA含量均为早期组最高（P<0.017）。结论 BA 肝纤维化早期TGF-β1、 Smad2促进纤维化至P-P、P-C型桥样结构形成；随着纤维化程度加重，TGF-β1、 Smad2表达促纤维化作用逐渐减弱。

关键词: 胆道闭锁, 转化生长因子β1, Smad2 蛋白质, 肝纤维化, 肝硬化

Abstract: Objective To observe the expression and function of TGF-β1 and Smad2 in liver fibrosis of biliary atresia. Methods Liver biopsy specimens were collected from autopsy(normal group, n=5), congenital biliary dilatation (CBD group, n=10), biliary atresia patients who undergoing Kasai procedure (Early hepatic fibrosis group, n=19), liver transplantation(transplantation group, n=11) ,the first three groups were collected from January 2010 to July 2014 in Tianjin childrens’ hospital, the last group was collected from January 2013 to January 2014 in Tianjin first central hospital. The hematoxylin ＆ eosin staining were used to observe the degree of liver fibrosis of every single sample, immunohistochemistry were used to observe the expression of TGF-β1 and Smad2 in liver tissues of these samples. At the same time, Quantitative Real-time Polymerase Chain Reaction was used to test the mRNA quantitative of TGF-β1 and Smad2 between these samples. Results HE: That the autopsy group showed no fibrosis, the CBD group had mild fiber cells hyperplasia, the Kasai group had severe fibrosis and the transplantation group had significant pseudolobule in the hematoxylin ＆ eosin staining. IHC: TGF-β1 was expressed in the cytoplasm of hepatocytes、bile duct cells、lymphocytes and neutrophils. The value of TGF-β1 average optical density was highest in the Kasai group and it had significant difference between four groups (P < 0.05); Smad2 was expressed in the cytoplasm of hepatocytes、bile duct cells、lymphocytes, and there were no difference between these four groups（P＞0.05）. qRT-PCR: Both TGF-β1mRNA and Smad2mRNA was different between these samples(P<0.017). Conclusion In early stage of BA,TGF-β1 and Smad2 made a contribution to liver fibrosis until the formation of P-P,P-C desmosome structure. However, after that while BA fibrosis became more serious, the pro-fibrogenic function of TGF-β1 and Smad2 became less.

Key words: biliary atresia , liver cirrhosis , transforming growth factor beta1 , Smad 2 protein, liver fibrosis