瘦素在胆道闭锁患儿肝纤维化中的表达及其临床意义

Clinical significance of expression of leptin in patients with biliary atresia and hepatic fibrosis

目的研究瘦素与胆道闭锁患儿肝纤维化的关系及其在胆道闭锁肝纤维化中的作用,为胆道闭锁患儿的治疗提供依据。方法回顾性分析2019年8月至2021年8月在天津市儿童医院普外科手术的胆道闭锁或先天性胆总管扩张症(CBD)患儿的临床资料。共纳入31例患儿,其中男性14例,女性17例,中位年龄[60(30,63)]d。胆道闭锁患儿26例作为研究组,CBD患儿5例作为对照组。免疫组织化学检测肝组织中瘦素蛋白、α-平滑肌肌动蛋白(α-SMA)以及磷酸化细胞外信号调节激酶1/2(p-ERK1/2)蛋白的表达情况。实时定量逆转录聚合酶链反应(qRT-PCR)检测肝组织中瘦素mRNA表达水平。结果研究组患儿肝组织中瘦素蛋白、α-SMA蛋白、p-ERK1/2蛋白的平均光密度值均高于对照组,差异有统计学意义(P<0.05)。瘦素、α-SMA以及p-ERK1/2在胆道闭锁患儿肝组织中的表达水平随纤维化程度的增加均同步升高,差异具有统计学意义(P<0.05)。瘦素在胆道闭锁患儿肝组织中表达水平与肝纤维化分级(rs=0.876)、α-SMA(r=0.723)和p-ERK1/2(r=0.725)均呈正相关(P<0.01)。qRT-PCR结果表明,胆道闭锁患儿肝组织中瘦素mRNA的含量高于CBD患儿,差异具有统计学意义(P<0.05)。结论瘦素的表达水平随着胆道闭锁肝纤维化程度的加重而升高。在胆道闭锁肝纤维化过程中,瘦素可能通过ERK1/2信号通路参与了HSCs活化。

Objective To study the relationship and the role of leptin in children with biliary atresia and hepatic fibrosis to provide a treatment basis for these patients.Methods The clinical data of children with biliary atresia or congenital biliary dilatation(CBD)who underwent surgical treatment at the Department of General Surgery of Tianjin Children's Hospital from August 2019 to August 2021 were retrospectively analyzed.Of 31 children included in this study,there were 14 males and 17 females,with age of 60(30,63)d.Children with biliary atresia served as the study group(n=26)and children with CBD served as the control group(n=5).Leptin protein,α-smooth muscleactin(α-SMA)and phosphorylation of extracellular-regulated protein kinase 1/2(p-ERK1/2)in liver tissues were detectd by immunohistochemistry(IHC).The expression level of leptin mRNA in liver tissues were detected by quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).Results The average optical density values of leptin protein,α-SMA protein and p-ERK1/2 protein in the liver tissues of children in the study group were significantly higher than the control group(P<0.05).The expression levels of leptin,α-SMA and p-ERK1/2 in liver tissues of children with biliary atresia significantly increased with increase in fibrosis degree(P<0.05).The expression level of leptin in liver tissues of children with biliary atresia was positively correlated with the liver fibrosis grade(rs=0.876),α-SMA(r=0.723)and p-ERK1/2(r=0.725)(P<0.01).The results of qRT-PCR showed that the content of leptin mRNA in liver tissues of children with biliary atresia was significantly higher than that of children with CBD(P<0.05).Conclusion Expressions of leptin increased with aggravation of degrees of hepatic fibrosis in biliary atresia.Leptin may be involved in activation of HSCs through the ERK1/2 signaling pathway in the process of hepatic fibrosis due to biliary atresia.