天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (7): 821-824.doi: 10.11958/20160362

• 专题研究·胆道闭锁与肝移植 • 上一篇    下一篇

整合素αvβ8、p38及ERK1/2在胆道闭锁患儿肝脏中的表达及意义

高婷 詹江华， 丁美云 ， 卫园园   

  1. 1 天津医科大学研究生院（邮编 300070）；2天津市儿童医院， 天津市儿科研究所
  • 收稿日期:2016-04-27 修回日期:2016-05-11 出版日期:2016-07-15 发布日期:2016-07-15
  • 通讯作者: 詹江华 E-mail:1158913136@qq.com
  • 作者简介:高婷（1989）， 女， 硕士在读， 主要从事小儿普外、胆道闭锁方面的研究
  • 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 expression and significance of integrin αvβ8, p38 and ERK1 /2 in the liver of children with biliary atresia

GAO Ting1， ZHAN Jianghua2△， DING Meiyun1， Wei Yuanyuan 1   

  1. 1 The Graduate School of Tianjin Medical University, Tianjin 300070, China; 2 Tianjin Children’ s Hospital, Tianjin Pediatrics Institute
  • Received:2016-04-27 Revised:2016-05-11 Published:2016-07-15 Online:2016-07-15
  • Contact: ZHAN Jianghua E-mail:1158913136@qq.com

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摘要： 目的 研究转化生长因子（TGF） -β1 通路相关调节蛋白整合素αvβ8、p38 及细胞外调节蛋白激酶 1/2（ERK1/2）蛋白在胆道闭锁（BA）患儿肝脏中的表达情况及在肝纤维化进程中的作用。 方法 选取天津市儿童医院普外科收治的 BA 患儿 15 例为 Kasai 组， 胆管扩张症患儿 10 例为胆扩组； 天津市第一中心医院小儿器官移植科行Kasai 手术后因肝功能衰竭行肝移植的 BA 患儿 10 例为肝移植组。 取患儿肝右叶前缘标本， 行 HE 染色观察肝纤维化程度， 行免疫组化染色检测αvβ8、p38 及 ERK1/2 在肝组织中的表达情况。 结果 HE 染色示， 胆扩组偶见纤维细胞增生； Kasai 组汇管区增宽， 纤维组织增生、桥接纤维化现象普遍， 可见假小叶形成； 移植组汇管区明显增宽， 纤维组织增生较重， 广泛桥接纤维组织形成， 假小叶明显。 免疫组化染色示， 胆扩组αvβ8 和ERK1/2 表达为弱阳性， p38为阴性表达； Kasai 组αvβ8、p38 及 ERK1/2 蛋白均在肝细胞胞质、汇管区胆管上皮细胞胞质及血管内皮细胞胞质中强阳性表达； 肝移植组αvβ8、p38 及 ERK1/2 蛋白皆为强阳性表达。 Kasai 组和肝移植组αvβ8、p38 及 ERK1/2 表达水平明显高于胆扩组（均 P＜ 0.05）， Kasai 组与肝移植组比较差异无统计学意义。 结论 αvβ8、p38 及 ERK1/2 表达在BA 肝纤维化过程中明显增高， αvβ8、p38 及 ERK1/2 可能参与并促进 BA 肝纤维进程。

关键词: 胆道闭锁, 肝硬化, p38 丝裂原活化蛋白激酶类, 丝裂原活化蛋白激酶 1, 肝纤维化, αvβ8, p38, ERK1/2

Abstract: Abstract： Objective To investigate the expression and significance of integrin αvβ8, p38 and extracellular signalregulated protein kinase 1/2 (ERK1/2) proteins, which are TGF- β1 pathway related regulatory protein, in liver fibrosis of children with biliary atresia (BA). Methods Fifteen cases of BA (Kasai group) and 10 cases of congenital biliary dilatation (CBD group) were collected in Tianjin Children’ s Hospital. And liver biopsy specimens were collected in Tianjin first central hospital, including 10 cases of BA children who underwent liver transplantation due to liver failure after Kasai operation (liver transplantation group). The specimens of front part of the right lobe of the liver were taken for HE and immunohistochemistry (IHC) staining. The expressions of αvβ8, p38 and ERK1/2 in liver were observed by IHC staining in three groups of liver tissues. Results HE staining showed fibroblast hyperplasia occasionally in CBD group, portal area expansion, fibrous tissue proliferation and wide spread bridging fibrosis with few pseudo lobules in Kasai group. In transplantation group, portal area was widened, the degree of fibrosis was severe and bridging fibrosis generally formed resulted in pseudo lobules widely. Imunohistochemistry showed that the expressions of αvβ8 and ERK1/2 were weakly positive, and the expression of p38 was negative in CBD group. In Kasai group, the expressions of αvβ8, p38 and ERK1/2 proteins were all strongly positive in liver cytoplasm, biliary epithelial cells and vascular endothelial cell cytoplasm. In liver transplantation group the expressions of αvβ8, p38 and ERK1/2 proteins were all strongly positive. The semi-quantitative analysis showed that the expressions levels of αvβ8, p38 and ERK1/2 were significantly higher in Kasai and liver transplantation groups than those of CBD group (P < 0.05). There were no significant differences in expression levels of αvβ 8, p38 and ERK1/2 between Kasai group and transplantation group (P > 0.05). Conclusion The expressions of αvβ8, p38 and ERK1/2 are gradually increased in liver of BA with the process of fibrosis, which indicate that they may be involved in the process of BA liver fibrosis.

Key words: biliary atresia, liver cirrhosis, p38 mitogen-activated protein kinases, mitogen-activated protein kinase 1, liver fibrosis, αvβ8, p38, ERK1/2