[1]颜培宏,郑一,陈后平,等. PAI-1 促进胆道闭锁肝纤维化的机制研究[J].临床小儿外科杂志,2018,17(10):790-794.
　Yan Peihong,Zheng Yi,Chen Houping,et al.Mechanism of plasminogen activator inhibitor1 promoting liver fibrosis in biliary atresia.[J].Journal of Clinical Pediatric Surgery,2018,17(10):790-794.
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 PAI-1 促进胆道闭锁肝纤维化的机制研究

《临床小儿外科杂志》[ISSN:1671-6353/CN:43-1380/R] 卷: 第17卷 期数: 2018年10期 页码: 790-794 栏目: 实验研究 出版日期: 2018-10-25
Title:
Mechanism of plasminogen activator inhibitor1 promoting liver fibrosis in biliary atresia.
作者:
 颜培宏; 郑一; 陈后平; 等
 贵阳市儿童医院小儿外科
Author(s):
Yan Peihong1; Zheng Yi1; Chen Houping1; Hou Lisong1; Zhu Li1; Ding Meiyun2; Zhan Jianghua2; Dong Chong3; Gao Wei3.
1.Department of Pediatric Surgery,Municipal Childrens Hospital,Guiyang 550003,China;
关键词:
 ; 胆道闭锁;  肝纤维化;  PAI1;  TGFβ1;  Smad3;  PSmad3
Keywords:
Biliary atresia;  Liver fibrosis;  PAI1;  TGFβ1;  Smad3;  PSmad3
文献标志码:
A
摘要:
 目的 探讨TGFβ1促纤维化信号通路中人纤溶酶原激活物抑制因子1(PAI1因子)在胆道闭锁肝组织中的表达规律，为揭示胆道闭锁肝纤维化机制提供理论依据。方法 收集2010年1月至2016年7月在天津市儿童医院诊治的患儿，分别为正常尸检死于非肝胆系统疾病5例（正常对照组）、胆道扩张症25例（胆扩组）、胆道闭锁Kasai手术25例（Kasai组）；同时收集2013年1月至2016年1月在天津市第一中心医院行肝移植手术患儿25例（移植组），通过HE染色观察组织结构、细胞形态、肝脏纤维化程度；通过免疫组化检测Smad3、PSmad3及PAI1表达。结果 HE染色结果：对照组肝脏无纤维化；胆扩组肝脏少许炎细胞浸润，少许纤维细胞增生，无胆管增生及明显纤维化；Kasai组肝脏纤维细胞、胶原纤维大量增生，出现大量桥接纤维化现象；移植组肝脏大量纤维组织增生，假小叶形成，肝硬化。免疫组化： ①四组中Kasai组Smad3、PSmad3及PAI1含量表达明显高于其他三组（P＜0.001），三种蛋白在Kasai组的表达与其他三组比较差异有统计学意义（P＜0.001）。②均值关系：Smad3含量高于PSmad3含量，而PSmad3与PAI1含量相当。③Kasai组肝小叶内PAI1含量(0.03±0.01)高于门管区(0.002±0.001)，差异具有统计学意义（t=13.76 ，P＜0.000）。结论 PAI1在Kasai组中表达最高，而在移植组中表达减低，说明其在胆道闭锁早期肝纤维化中具有促纤维化作用，随着肝纤维化程度加重，其促纤维化作用逐渐减低。
Abstract:
ObjectiveTo explore the expression of plasminogen activator inhibitor1 (PAI1) of transforming growth factor beta 1 (TGFβ1) profibrotic signaling pathway in liver of biliary atresia (BA) and provide theoretical rationales for elucidating the mechanism of liver fibrosis in BA.MethodsA total of 55 children diagnosed and treated at Tianjin Childrens Hospital from January 2010 to July 2016 were divided into three groups,including those dying of normal nonhepatobiliary diseases (control group,n=5),congenital biliary dilatation (biliary dilatation group,n=25) and Kasai operation with biliary atresia (Kasai group,n=25).And another 25 patients underwent liver transplantation at First Central Municipal Hospital of Tianjin from January 2013 to January 2016 (transplantation group,n=25).The tissue structure and the degree of liver fibrosis were observed by hematoxylin & eosin (HE) staining.And immunohistochemical staining was used for detecting the expressions of Smad3,PSmad3 and PAI1. ResultsHE staining showed that there was no fibrosis in liver in control group.There were a few inflammatory cells and fibroblast proliferation in biliary dilatation group and without bile duct hyperplasia and obvious fibrosis.In Kasai group,fibroblasts and collagen fibers proliferated extensively and bridging fibrosis occurred.In transplantation group,massive fibrous tissue hyperplasia,pseudolobular formation and cirrhosis could be found.Immunohistochemical staining showed that the expressions of Smad3,PSmad3 and PAI1 in Kasai group were significantly higher than three other groups (P<0.000).The differences were statistically significantly.Smad3 content was higher than PSmad3 content while PSmad3 was equivalent to PAI1.The PAI1 content (0.03±0.01) in hepatic lobules of Kasai group was higher than that in portal area (0.002±0.001) (t=13.76,P<0.000).The differences was statistically significant.ConclusionPAI1 is mostly expressed in Kasai group and decreases in transplantation group.It implies that PAI1 has profibrotic effect on early stage of BA.As the degree of liver fibrosis advances,profibrotic effect gradually subdues.

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更新日期/Last Update: 2018-10-24