Alimujiang·Abudureyimu,Lin Feng,Wang Haojie,et al.Activation of Notch signaling pathway collaborated with macrophages for promoting liver fibrosis in biliary atresia[J].Journal of Clinical Pediatric Surgery,2021,20(04):376-381.[doi:10.12260/lcxewkzz.2021.04.014]
Notch信号通路活化协同巨噬细胞对胆道闭锁肝纤维化的作用研究
- Title:
- Activation of Notch signaling pathway collaborated with macrophages for promoting liver fibrosis in biliary atresia
- Keywords:
- Biliary Atresia/ET; Liver Cirrhosis/CO; Liver Cirrhosis/ET; Notch Signaling Pathway; Macrophages
- 分类号:
- R726;R657.4+4
- 摘要:
- 目的 探究Notch信号通路活化及相关炎性反应分子机制在胆道闭锁患者肝纤维化进展中的作用。方法 选取2019年1月至2020年11月于天津市儿童医院确诊的20例胆道畸形患者(15例胆道闭锁,5例胆总管扩张)作为研究对象,收集临床资料及术中留取的肝活检组织样本,使用免疫组化方法检测患者肝组织内Notch信号通路的效应分子HES-1,M2型巨噬细胞标志物CD163及细胞因子IL-6、PDGF-AA的表达并进行半定量分析。结果 与胆总管扩张组相比,HES-1(0.044±0.017 vs.0.143±0.027)、CD163(0.089±0.020 vs.0.259±0.111)、IL-6(0.070±0.007 vs.0.216±0.028)、PDGF-AA (0.155±0.019 vs.0.220±0.044)在胆道闭锁患者肝组织中的表达明显增加,且差异有统计学意义(P<0.05);HES-1的表达与CD163的表达呈正相关(rs=0.687,P<0.01);HES-1、CD163、IL-6、PDGF-AA与肝纤维化程度成明显正相关(rs=0.791,rs=0.912,rs=0.920,rs=0.887,P<0.001)。结论 Notch信号通路参与了胆道闭锁肝纤维化进程,并与M2型巨噬细胞有协同作用。
- Abstract:
- Objective To explore the relationship of activation of Notch signaling pathway with related inflammatory molecular mechanisms in fibrotic progression of children with biliary atresia (BA).Methods From January 2019 to November 2020, 20 children of biliary malformation were recruited from Tianjin Children’s Hospital.The causes were BA (n=15) and congenital biliary dilatation (CBD, n=5).Intraoperative liver biopsy samples were collected.HES-1, an effector molecule of Notch signaling pathway, and M2 macrophage marker CD163, cytokines IL-6 and PDGF-AA in liver tissue were detected by immunohistochemistry.Results As compared with CBD, the expression of HES-1, CD163, IL-6 and PDGF-AA in the liver tissues of children with BA markedly increased (0.044±0.017 vs.0.143±0.027) (0.089±0.020 vs.0.259±0.111) (0.070±0.007 vs.0.216±0.028) (0.155±0.019 vs.0.220±0.044).The expression of HES-1 was positively correlated with the expression of CD163 (r=0.687, P<0.01).And HES-1, CD163, IL-6 and PDGF-AA were positively correlated with the extent of liver fibrosis (rs=0.791, rs=0.912, rs=0.920, rs=0.887, P<0.001). Conclusion Involved in the process of hepatic fibrosis in biliary atresia, Notch signaling pathway has a synergistic effect with M2 macrophages.
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备注/Memo
收稿日期:2020-12-31。
基金项目:新疆维吾尔自治区自然科学基金(编号:2019D01A12)
作者简介:阿里木江·阿不都热依木,Email:alm0223@163.com