Notch-1、Jagged-1、Hes-1在胆道闭锁患儿肝纤维化中的表达及意义

Expression and significance of Notch-1, Jagged-1 and Hes-1 in liver fibrosis of children with biliary atresia

目的探讨Notch信号通路在胆道闭锁(biliary atresia ,BA)肝纤维化进程中的作用。方法根据Ohkuma’s肝纤维化分级标准选取2014年6月至2017年12月就诊于天津市儿童医院普外科的胆道闭锁患儿40例作为BA组,并将其分为4个亚组;另选取先天性胆管扩张症(CBD)患儿5例作为CBD组;采用正常肝脏组织样本5例作为对照组。用免疫组化方法检测肝脏组织中的Notch通路元件(包括Notch1受体、Jagged1配体、Hes1靶基因)的表达量。结果①免疫组化定性结果:Notch1在BA组强阳性表达,CBD组阳性表达,对照组弱阳性表达;Jagged1在BA组阳性表达,CBD组和对照组弱阳性表达;Hes1在BA组和CBD组阳性表达,对照组弱阳性表达;②免疫组化半定量结果:Notch-1、Jagged-1、Hes-1在BA组与对照组表达情况分别是(0.174±0.037比0.054±0.004,P<0.001)、(0.182±0.055比0.048±0.010,P<0.001)、(0.148±0.050比0.050±0.023,P<0.001),BA患儿肝组织表达均高于对照组,差异具有统计学意义。Notch-1、Jagged-1、Hes-1在BA组与CBD组的表达情况是(0.174±0.037比0.191±0.318,P>0.05)、(0.182±0.055比0.260±0.061,P>0.05)、(0.148±0.050比0.108±0.018,P<0.05),Notch-1与Jagged-1在两组的差异无统计学意义,Hes-1在两组中的差异具有统计学意义。而在BA组中,Notch通路元件的表达量均随纤维化程度加重而升高(Notch-1: F=31.215, P<0.001;Jagged-1: F=13.914, P<0.001;Hes-1=66.127, P<0.001)。结论Notch信号通路元件在肝组织内异常活化可能参与胆道闭锁肝纤维化进程。

Objective To explore the role of Notch signaling pathway in the progression of biliary atresia (BA) in liver fibrosis.Methods According to the Ohkuma's grading standard of liver fibrosis,40 hospitalized BA children at Municipal Children's Hospital from June 2014 to December 2017 were divided into 4 subgroups (n=10 each);children with congenital biliary dilatation (CBD)(n=5);normal liver tissue samples (n=5).The expression levels of Notch pathway elements (including Notch-1 receptor,Jagged-1 ligand & Hes-1 target gene) in liver tissues were detected by immunohistochemistry.Results ① Immunohistochemical qualitative results: Notch-1 was strongly expressed in BA group,positive expression in CBD group and weak expression in control group;Jagged-1 was positive in BA group and weak expression in CBD and control groups;Hes-1 gene was positively expressed in BA and CBD groups and weak positive expression in control group;②Immunohistochemical semi-quantitative results: expressions of Notch-1,Jagged-1 and Hes-1 in BA and control groups were (0.174±0.037 vs.0.054±0.004,P<0.001),(0.182±0.055 vs.0.048±0.010,P,respectively)<0.001),(0.148±0.050 vs 0.050±0.023,P<0.001).The expressions in liver tissue of BA children were higher than those in control group with statistical differences.The expressions of Notch-1,Jagged-1 and Hes-1 in BA and CBD groups were (0.174±0.037 vs.0.191±0.318,P>0.05),(0.182±0.055 vs.0.260±0.061,P>0.05) and (0.148±0.050 vs.0.108±0.018,P<0.05).No significant inter-group difference existed in Notch-1 or Jagged-1.The difference between Hes-1 group and control was statistically significant.In BA subgroup,the expression level of Notch pathway elements increased with the advancing degree of fibrosis (Notch-1: F=31.215,P<0.001;Jagged-1: F=13.914,P<0.001;Hes-1=66.127,P<0.001).Conclusions Abnormal activation of Notch signaling pathway elements in liver tissue may be involved in the progression of BA.