胆道闭锁小儿肝组织MMP-2和TGF-β1表达及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2023.04.034

摘要/Abstract

摘要： 目的探讨胆道闭锁(BA)患儿肝组织基质金属蛋白酶2(MMP-2)和转化生长因子-β1(TGF-β1)表达及其临床意义。方法 2017年4月～2020年4月我院诊治的49例BA患儿和44例胆总管囊肿(CCC)患儿,均行Kasai手术,术后随访2年。常规行肝组织病理学检查,采用SP法检测肝组织MMP-2和TGF-β1表达。应用Kaplan-Meier法绘制生存曲线。结果 BA患儿肝组织MMP-2和TGF-β1表达相对水平分别为(0.3±0.1)和(3.3±0.5),显著强于CCC患儿【分别为(0.1±0.0)和(1.1±0.2),P<0.05】;8例Ⅳ期肝纤维化BA患儿肝组织MMP-2⁺⁺⁺阳性率为62.5%,8例Ⅲ期BA患儿为62.5%,均显著高于Ⅰ期的14.3%或Ⅱ期的15.8%(P＜0.05);Ⅳ期肝纤维化BA患儿肝组织TGF-β1⁺⁺⁺阳性率为87.5%,Ⅲ期BA患儿为62.5%,均显著高于Ⅰ期的0.0%或Ⅱ期的0.0%(P＜0.05);术后失访4例,自体肝生存19例(42.2%);肝组织MMP-2⁺阳性患儿自体肝生存率为75.0%(9/12),MMP-2⁺⁺阳性患儿为47.4%(9/19),MMP-2⁺⁺⁺阳性患儿为7.1%(1/14);肝组织TGF-β1⁺阳性患儿自体肝生存率为86.7%(13/15),TGF-β1⁺⁺阳性患儿自体肝生存率为22.2%(4/18),TGF-β1⁺⁺⁺阳性患儿为16.7%(2/12)。经Kaplan-Meier生存分析显示,肝组织MMP-2和TGF-β1低表达患儿自体肝生存率显著高于高表达患儿(x²=15.357,P=0.000;x²=14.704,P=0.001)。结论 BA患儿肝组织MMP-2和TGF-β1呈高表达倾向,而MMP-2和TGF-β1表达与肝纤维化分期相关,高表达者预示术后生存期较短,值得进一步探讨。

关键词: 胆道闭锁, Kasai术, 基质金属蛋白酶2, 转化生长因子-β1, 肝纤维化, 预后, 儿童

Abstract: Objective The aim of this study was to investigate the implication of liver tissue matrix metalloproteinase-2 (MMP-2) and transforming growth factor-β1 (TGF-β1) expression in children with biliary atresia (BA). Methods 49 children with BA and 44 children with choledochal cyst (CCC) were admitted to our hospital between April 2017 and April 2020, and all the children with BA or with CCC underwent Kasai surgery. All the children were followed-up for 2 years. The hepatic MMP-2 and TGF-β1 expression was detected by SP immunohistochemical staining. The Kaplan-Meier was applied to compare the prognosis of children with BA. Results The relative hepatic expression of MMP-2 and TGF-β1 in children with BA were (0.3±0.1) and (3.3±0.5), significantly stronger than [(0.1±0.0) and (1.1±0.2),respectively, P<0.05] in children with CCC; the strong positive rate of hepatic MMP-2 in 8 children with liver fibrosis stage Ⅳ was 62.5% and in another 8 children with stage Ⅲ was also 62.5%, both significantly higher than 14.3% in children with stage Ⅰ or 15.8%(P＜0.05) in children with stage Ⅱ; the strong positive rate of hepatic TGF-β1 in children with stage Ⅳ was 87.5%, and in children with stage Ⅲ was 62.5%, both much higher than 0.0% in with stage Ⅰ or 0.0%(P＜0.05) in with stage Ⅱ; 4 children lost visit at the end of two year follow-up, and 19 children (42.2%)survived in our series; the survival rate in children with weak hepatic MMP-2 positive was 75.0%(9/12), in children with moderate MMP-2 positive was 47.4%(9/19), and in with strong MMP-2 positive was 7.1%(1/14); the survival in children with weak hepatic TGF-β1 positive was 86.7%(13/15), in with moderate TGF-β1 positive was 22.2%(4/18), and in with strong TGF-β1 positive was 16.7%(2/12), suggesting that the survival in child with weak hepatic MMP-2 and TGF-β1 expression was significantly higher than in those with strong expression (Kaplan-Meier analysis, x²=15.357, P=0.000; x²=14.704, P=0.001). Conclusion The expression of MMP-2 and TGF-β1 in liver tissues of children with BA is highly correlated to liver fibrosis, and the children with strong MMP-2 and TGF-β1 expression might have a poor prognosis, which warrants further investigation.

Key words: Biliary atresia, Kasai surgery, Matrix metalloproteinase-2, Transforming growth factor-β1, Liver fibrosis, Prognosis, Children

周盈营, 赵斌, 信学礼, 刘亚彬. 胆道闭锁小儿肝组织MMP-2和TGF-β1表达及其临床意义探讨^*[J]. 实用肝脏病杂志, 2023, 26(4): 588-591.

Zhou Yingying, Zhao Bin, Xin Xueli, et al. Implication of liver tissue MMP-2 and TGF-β1 expression in children with biliary atresia[J]. Journal of Practical Hepatology, 2023, 26(4): 588-591.

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胆道闭锁小儿肝组织MMP-2和TGF-β1表达及其临床意义探讨^*

Implication of liver tissue MMP-2 and TGF-β1 expression in children with biliary atresia

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