自身免疫性肝炎患儿外周血单个核细胞miRNA-181c表达与干扰素γ、趋化因子配体10、Toll样受体4的相关性分析

Correlation of miRNA-181c expression in peripheral blood mononuclear cells with interferon-γ,chemokine(C-X-C motif)ligand 10,and Toll-like receptor 4 in children with autoimmune hepatitis

目的探讨儿童自身免疫性肝炎(AIH)患者外周血单个核细胞(PBMC)miRNA-181c表达与干扰素γ(IFNγ)、趋化因子配体10(CXCL10)、Toll样受体4(TLR4)的相关性。方法选取2015年3月-2019年5月延边大学附属医院收治的儿童AIH 27例作为AIH组,另选取同期健康体检儿童30例作为对照组,检测两组儿童PBMC miRNA-181c及IFNγ、CXCL10、TLR4表达情况。符合正态分布的计量资料两组间比较采用t检验;非正态分布的计量资料两组间比较采用Wilcoxon秩和检验。计数资料两组间比较采用χ^2检验。采用Pearson相关系数分析miRNA-181c表达与各指标的相关性。采用logistic回归分析各因素对AIH的影响。结果AIH组患儿肝功能指标AST、ALT、GGT及TBil水平均高于对照组,差异有统计学意义(t值分别为14.445、20.064、11.728、13.822,P值均<0.001)。AIH组患儿IgA、IgM及IgG水平均明显高于对照组(t值分别为7.772、5.147、6.771,P值均<0.05)。AIH组患儿PBMC miRNA-181c相对表达量低于对照组,差异有统计学意义(0.784±0.173 vs 1.106±0.224,t=5.819,P<0.05)。AIH组患儿IFNγ、CXCL10及TLR4 mRNA表达水平均明显高于对照组(t值分别为6.949、12.303、13.835,P值均<0.05)。相关性分析结果显示,AIH患儿PBMC miRNA-181c表达与IFNγ、CXCL10、TLR4、AST、ALT、GGT、TBil及IgG呈负相关(r值分别为-0.316、-0.348、-0.322、-0.427、-0.442、-0.408、-0.396、-0.321,P值均<0.05)logistic单因素回归分析结果显示,AST、ALT、GGT、TBil、IFNγ、CXCL10、TLR4 mRNA及miRNA-181c均进入回归模型(P值均<0.05),是AIH发生的影响因素。结论儿童AIH患者表现出PBMC miRNA-181c表达的下调,且该异常表达与IFNγ、CXCL10、TLR4等免疫细胞因子密切相关,提示miRNA-181c可能通过对免疫系统的调控影响儿童AIH的发生。

Objective To investigate the correlation of miR-181c expression in peripheral blood mononuclear cells(PBMCs)with interferon-γ(IFN-γ),chemokine(C-X-C motif)ligand 10(CXCL10),and Toll-like receptor 4(TLR4)in children with autoimmune hepatitis(AIH).Methods A total of 27 children with AIH who were admitted to The Affiliated Hospital of Yanbian University from March 2015 to May 2019 were enrolled as AIH group,and 30 healthy children who underwent physical examination during the same period of were enrolled as control group.The expression of miR-181c in PBMCs and the expression of IFN-γ,CXCL10,and TLR4 were measured for the two groups.The t-test was used for comparison of normally distributed continuous data between two groups,and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Pearson correlation coefficient was used to investigate the correlation of miR-181c expression with each index,and a logistic regression analysis was used to investigate the influence of each factor on AIH.Results Compared with the control group,the AIH group had significantly higher levels of the liver function parameters aspartate aminotransferase(AST),alanine aminotransferase(ALT),gamma-glutamyl transpeptidase(GGT),and total bilirubin(TBil)(t=14.445,20.064,11.728,13.822,all P<0.001).The AIH group also had significantly higher levels of IgA,IgM,and IgG than the control group(t=7.772,5.147,and 6.771,all P<0.05).The AIH group had significantly lower relative expression of miR-181c in PBMCs than the control group(0.784±0.173 vs 1.106±0.224,t=5.819,P<0.05).Compared with the control group,the AIH group had significantly higher levels of IFN-γand CXCL10 and mRNA expression of TLR4(t=6.949,12.303,and 13.835,all P<0.05).The correlation analysis showed that in the children with AIH,the expression of miR-181c in PBMCs was negatively correlated with IFN-γ,CXCL10,TLR4,AST,ALT,GGT,TBil,and IgG(r=-0.316,-0.348,-0.322,-0.427,-0.442,-0.408,-0.396,and-0.321,all P<0.05).The univariate logistic regression analysis showed that AST,ALT,GGT,TBil,IFN-γ,CXCL10,TLR4 mRNA,and miR-181c were all included in the regression model(all P<0.05)and were the influencing factors for the onset of AIH.Conclusion Children with AIH have downregulated expression of miR-181c in PBMCs,which is closely associated with IFN-γ,CXCL10,and TLR4,suggesting that miR-181c may affect the development of AIH in children by regulating the immune system.