吉林大学学报(医学版) ›› 2021, Vol. 47 ›› Issue (5): 1237-1243.doi: 10.13481/j.1671-587X.20210522

• 临床研究 • 上一篇    下一篇

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

吴宙光,王斌(),程珍,张文杰,左桃燕,陈思琦,付静茹   

  1. 深圳市儿童医院普外科,广东 深圳 518026
  • 收稿日期:2021-02-05 出版日期:2021-09-28 发布日期:2021-10-26
  • 通讯作者: 王斌 E-mail:zhwuzhouguang@163.com
  • 作者简介:吴宙光(1979-),男,广东省中山市人,副主任医师,医学博士,主要从事小儿微创普通外科基础与临床方面的研究。
  • 基金资助:
    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)

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

Zhouguang WU,Bin WANG(),Zhen CHENG,Wenjie ZHANG,Taoyan ZUO,Siqi CHEN,Jingru FU   

  1. Department of General Surgery,Shenzhen Children’s Hospital,Guangdong Province,Shenzhen 518026,China
  • Received:2021-02-05 Online:2021-09-28 Published:2021-10-26
  • Contact: Bin WANG E-mail:zhwuzhouguang@163.com

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-SMA mRNA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-SMA mRNA表达水平明显升高(P<0.05),BA患儿肝组织中GPC3 与α-SMA mRNA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。

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

Abstract: Objective

To investigate the expressions of phosphatidylinositol proteoglycan 3 (GPC3) and α-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 and α-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 and α-SMA mRNA and the correlations of GPC3 and α-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) and γ-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 and α-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 and α-SMA mRNA in liver tissue of the children in BA group were significantly increased (P<0.05);there was a positive relationship between GPC3 and α-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, and α-SMA protein expression was positive in 20 (76.9%) cases of BA children.Compared with control group, the expression levels of GPC3 and α-SMA proteins in liver tissue of the children in BA group were increased (P<0.05).The Pearson correlation analysis results showed that the GPC-3 protein expression level was positively correlated with ALP level (r=0.582, P=0.008) and Metavir score (r=0.468,P=0.016),and it was negatively correlated with age (r=-0.384,P=0.026),ALB level (r=-0.514,P=0.005) and AST level (r=-0.327 2,P=0.035).The α-SMA protein expression level was positively correlated with ALP level (r=0.465,P=0.016) and Metavir score (r=0.422,P=0.010). Compared with good prognosis group, the expression levels of GPC3 and α-SMA proteins and Metavir score in liver tissue of the children in poor prognosis group were significantly increased (P<0.05).

Conclusion

The high expression levels of GPC3 and α-SMA in the liver tissue may be positively correlated with the degrees of liver dysfunction and fibrosis in the BA children, which often suggests a poor prognosis.

Key words: biliary atresia, phosphatidylinositol proteoglycan 3, alphα-smooth muscle actin, liver function, liver fibrosis

中图分类号: 

  • R722