钙黏蛋白-11在胆道闭锁患儿肝组织中的表达及意义

doi:10.12372/jcp.2022.21e1058

摘要/Abstract

摘要：

目的分析钙黏蛋白-11（cadherin-11,CDH11）在胆道闭锁（biliary atresia,BA）患儿肝组织内的表达及意义。方法选取2014年11月至2016年12月就诊的BA和胆总管囊肿（CC）患儿作为研究对象。分析患儿肝脏CDH11与肝纤维化标志基因和血清肝功能指标的相关性。结果 BA组50例,女25例、男25例,中位年龄59.5（46.8~71.8）天;CC组8例,女5例、男3例,中位年龄70.0（49.0~125.3）天。BA组患儿肝脏中CDH11 mRNA表达水平显著高于CC组,差异有统计学意义（P<0.01）。BA肝内CDH11 mRNA表达水平与转化生长因子β1（TGFB1）、转化生长因子β2（TGFB2）、角蛋白19（KRT19）、肌动蛋白α2（ACTA2）、Ⅰ型胶原α1链（COL1A1）和Ⅳ型胶原α1链（COL4A1） mRNA表达水平呈显著正相关（r= 0.36~0.73,P均<0.01）。与轻度肝纤维化BA患儿相比,CDH11表达水平在重度肝纤维化BA患儿肝内显著升高（P<0.01）。BA肝内CDH11 mRNA表达水平与血清γ-谷氨酰转肽酶（γ-GT）、总胆红素（TBil）、直接胆红素（DBil）和胆汁酸（TBA）水平呈正相关（r=0.26~0.37,P均<0.05）。结论与CC患儿相比,CDH11在BA患儿肝组织中表达水平显著升高。BA肝内CDH11表达水平与肝纤维化进程和肝脏损伤程度密切相关。

关键词: 胆道闭锁, 钙黏蛋白-11, 肝纤维化, 肝损伤

Abstract:

Objective To analyze the expression and significance of cadherin-11 (CDH11) in livers of children with biliary atresia (BA). Methods Fifty children with BA and eight children with choledochal cyst (CC) were selected as the research objects. The expression levels of CDH11 and liver fibrotic marker genes in the livers of the children were evaluated by quantitative real-time polymerase chain reaction. The correlation between CDH11 and liver fibrotic marker genes or serum liver function markers was analyzed. Results The mRNA levels of CDH11 were significantly elevated in livers of children with BA compared to children with CC (P< 0.01). Hepatic CDH11 mRNA levels were positively correlated with the expression levels of transforming growth factor beta 1, transforming growth factor beta 2, keratin 19, actin alpha 2, smooth muscle, collagen type I alpha 1 and collagen type IV alpha 1 in children with BA (r= 0.36 ~ 0.73, all P< 0.01). The mRNA levels of CDH11 in livers of BA patients with severe liver fibrosis significantly increased compared to BA patients with mild liver fibrosis (P< 0.01). Hepatic CDH11 mRNA levels were positively correlated with serum levels of γ-glutamyl transferase, total bilirubin, direct bilirubin and bile acid in children with BA (r= 0.26 ~ 0.37, all P< 0.05). Conclusions The mRNA levels of CDH11 were significantly increased in livers of BA patients compared to CC patients. The expression levels of CDH11 were associated with the progression of liver fibrosis and degree of liver injury in BA.

Key words: biliary atresia, cadherin-11, liver fibrosis, liver injury

吴博, 田心蓓, 卢颖, 杜君, 肖永陶. 钙黏蛋白-11在胆道闭锁患儿肝组织中的表达及意义[J]. 临床儿科杂志, 2022, 40(2): 134-138.

WU Bo, TIAN Xinbei, LU Ying, DU Jun, XIAO Yongtao. Expression and significance of cadherin-11 in liver of children with biliary atresia[J]. Journal of Clinical Pediatrics, 2022, 40(2): 134-138.

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参考文献 19

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基因	引物方向	引物序列
CDH11	正向(5'-3')	TCAAGGGCCCCAGAAATCAC
CDH11	反向(5'-3')	CGCAGACCTCTCTTGGGATG
COL1A1	正向(5'-3')	GGACACAGAGGTTTCAGTGGT
COL1A1	反向(5'-3')	GCACCATCATTTCCACGAGC
COL4A1	正向(5'-3')	GCCCTTCTGCTCCACGAG
COL4A1	反向(5'-3')	CGGAGGTCCTCTTGTCCCTT
TGFB1	正向(5'-3')	ACTATTGCTTCAGCTCCACG
TGFB1	反向(5'-3')	CCCGGGTTATGCTGGTTGTA
TGFB2	正向(5'-3')	GCTCTGTGGGTACCTTGATGC
TGFB2	反向(5'-3')	GCGCTGGGTTGGAGATGTTA
ACTA2	正向(5'-3')	TATCCCCGGGACTAAGACGG
ACTA2	反向(5'-3')	CACCATCACCCCCTGATGTC
KRT19	正向(5'-3')	GGGCAACGAGAAGCTAACCA
KRT19	反向(5'-3')	AGACGGGCATTGTCGATCTG
HPRT1	正向(5'-3')	GCTTTCCTTGGTCAGGCAGT
HPRT1	反向(5'-3')	GCTTGCGACCTTGACCATCT

基因	BA组(n=50)	CC组(n=8)	Z值	P
CDH11	1.9(1.3~2.7)	1.0(0.7~1.3)	3.04	0.002
TGFB1	1.9(1.5~2.4)	0.7(0.4~1.5)	3.07	0.002
TGFB2	2.4(1.3~3.7)	0.8(0.4~1.3)	3.04	0.002
KRT19	3.0(1.6~5.4)	0.7(0.6~1.1)	3.25	0.001
ACTA2	2.5(1.8~3.4)	0.8(0.6~1.1)	3.68	< 0.001
COL1A1	1.5(1.1~1.8)	0.9(0.3~1.2)	2.44	0.015
COL4A1	1.6(1.0~2.1)	0.9(0.3~1.4)	2.35	0.019

项目	BA组(n=50)	CC组(n=8)	Z值	P
ALT/U·L^-1	120.5(79.3~176.3)	49.0(26.3~127.8)	2.48	0.013
AST/U·L^-1	204.5(135.0~278.3)	62.5(42.0~202.5)	2.81	0.005
γ-GT/U·L^-1	460.0(227.5~721.3)	86.5(23.0~300.5)	3.22	0.001
TBil/μmol·L^-1	138.5(115.8~181.8)	18.5(6.0~56.8)	4.50	< 0.001
DBil/μmol·L^-1	96.5(74.3~123.4)	3.5(1.5~27.3)	4.49	< 0.001
TBA/μmol·L^-1	101.9(77.2~126.5)	10.0(5.5~97.8)	2.51	0.012