胆道闭锁患儿肝组织中GPC3和α-SMA表达与肝功能指标的相关性分析  

Analysis on correlation of GPC3 andα-SMA expressions with liver function-related indexes in liver tissue of children with biliary atresia

作　　者：吴宙光[1] 王斌[1] 程珍 张文杰 左桃燕 陈思琦 付静茹 WU Zhouguang;WANG Bin;CHENG Zhen;ZHANG Wenjie;ZUO Taoyan;CHEN Siqi;FU Jingru(Department of General Surgery,Shenzhen Children’s Hospital,Guangdong Province,Shenzhen 518026,China)

机构地区：[1]深圳市儿童医院普外科,广东深圳518026

出　　处：《吉林大学学报（医学版）》2021年第5期1237-1243,共7页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金项目(81770512);广东省深圳市卫健委医疗卫生三名工程项目(SZSM201812055)。

摘　　要：目的:探讨胆道闭锁(BA)患儿磷脂酰肌醇蛋白聚糖3(GPC3)和α-平滑肌肌动蛋白(α-SMA)的表达,并阐明其与肝功能指标的相关性。方法:选择26例BA患儿作为研究对象(BA组),所有患儿均行Kasai术,选择20例胆总管囊肿患儿为对照组。采用实时荧光定量PCR(RT-qPCR)和免疫组织化学法检测2组患儿肝组织中GPC3和α-SMAmRNA和蛋白表达水平;采用Pearson相关分析法分析BA组患儿肝组织中GPC3和α-SMA蛋白表达水平与患儿肝功能指标[白蛋白(ALB)、总胆红素(TB)、直接胆红素(DB)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)和γ-谷氨酰转氨酶(γ-GGT)]的相关性。术后随访6个月后根据肝功能水平分为预后良好组18例和预后不良组8例,比较不同预后组患儿GPC3和α-SMA蛋白表达水平,采用Metavir评分比较不同预后组患儿肝纤维化程度。结果:与对照组比较,BA组患儿肝组织中GPC3和α-SMAmRNA表达水平明显升高(P<0.05),BA患儿肝组织中GPC3与α-SMAmRNA表达水平呈正相关关系(r=0.537,P=0.005)。BA患儿中,21例(80.8%)BA患儿GPC3蛋白表达阳性,20例(76.9%)BA患儿α-SMA蛋白表达阳性,与对照组比较,BA组患儿肝组织中GPC3和α-SMA蛋白表达水平升高(P<0.05)。Pearson相关分析,BA患儿肝组织中GPC3蛋白表达水平与ALP水平(r=0.582,P=0.008)、Metavir评分(r=0.468,P=0.016)呈正相关关系,与年龄(r=-0.384,P=0.026)、ALB水平(r=-0.514,P=0.005)和AST水平(r=-0.327,P=0.035)呈负相关关系;α-SMA蛋白表达水平与ALP水平(r=0.465,P=0.016)和Metavir评分(r=0.422,P=0.010)呈正相关关系。与预后良好组比较,预后不良组患儿肝组织中GPC3和α-SMA蛋白表达水平及Metavir评分明显升高(P<0.05)。结论:肝组织中GPC3和α-SMA的高水平表达可能与BA患儿肝功能障碍和肝纤维化程度呈正相关关系,多提示预后不良。Objective:To investigate the expressions of phosphatidylinositol proteoglycan 3(GPC3)andα-smooth muscle actin(α-SMA)in the liver tissue of the biliary atresia(BA)children,and to investigate their correlations with liver function related indexes.Methods:A total of 26 children with BA were selected as the study subjects(BA group).All patients received Kasai surgery.Twenty children with choledochal cyst were selected as control group.Real-time fluorescence quantitative PCR(RT-qPCR)and immunohistochemistry were used to detect the expression levels of GPC3 andα-SMA mRNA and proteins in liver tissue of the patients in two groups;Pearson correlation analysis was used to analyze the correlations of the GPC3 mRNA expression level with the expression level of andα-SMA mRNA and the correlations of GPC3 andα-SMA protein expression levels in liver tissue and liver function indexes[albumin(ALB),total bilirubin(TB),direct bilirubin(DB),alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)andγ-glutamyl aminotransferase(γ-GGT)]of the patients.After 6 months of postoperative follow-up,18 patients were divided into good prognosis group and 8 patients were divided into poor prognosis group according to the level of liver function.The protein expression levels of GPC3 andα-SMA of the patients in different prognosis groups were compared.Metavir score was used to compare the degrees of liver fibrosis patients in different prognosis groups.Results:Compared with control group,the expression levels of GPC3 andα-SMA mRNA in liver tissue of the children in BA group were significantly increased(P<0.05);there was a positive relationship between GPC3 andα-SMA mRNA expression levels in liver tissue of the BA children(r=0.5370,P=0.005).GPC3 protein expression was positive in 21(80.8%)cases of BA children,andα-SMA protein expression was positive in 20(76.9%)cases of BA children.Compared with control group,the expression levels of GPC3 andα-SMA proteins in liver tissue of the children in BA group were

关 键 词：胆道闭锁 磷脂酰肌醇蛋白聚糖3 Α平滑肌肌动蛋白 肝功能 肝纤维化 

分 类 号：R722[医药卫生—儿科]