microRNA-18a通过PPARαγ信号通路上调慢性乙型肝炎患者调节性免疫功能

叶军; 韩山山; 卢盺奕; 商玉涛; 冯志强

doi:10.3969/j.issn.1001-5256.2020.05.015

microRNA-18a通过PPARαγ信号通路上调慢性乙型肝炎患者调节性免疫功能

DOI: 10.3969/j.issn.1001-5256.2020.05.015

1. 安徽医科大学空军临床学院肝胆外科
2. 空军特色医学中心肝胆外科
3. 安徽医科大学药学院创新药物研究所
4. 北京朝阳急诊抢救中心普通外科

基金项目:

国家自然科学基金项目（81341067）；第7批博士后科学基金特别项目（2014T71010）；

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中图分类号: R512.62
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出版历程
- 收稿日期: 2019-12-17
- 出版日期: 2020-05-20

microRNA-18a upregulates the regulatory immune function in patients with chronic hepatitis B through the PPARα/γ signaling pathway

Department of Hepatobiliary Surgery,Clinical College of Air force,Anhui Medical University

Research funding:

摘要

摘要:
目的分析microRNA-18a（miRNA-18a）通过过氧化物酶体增殖物激活受体α/γ（PPARα/γ）信号通路对慢性乙型肝炎患者调节性免疫功能的影响。方法纳入空军特色医学中心（原中国人民解放军空军总医院）2017年4月-2018年10月98例慢性乙型肝炎患者和96例非乙型肝炎患者分别作为试验组和对照组。实时荧光定量聚合酶链反应检测2组患者血清中的miRNA-18a mRNA的相对表达量;流式细胞技术检测人外周血单个核细胞中miRNA-18a的表达;酶联免疫吸附试验检测miRNA-18a对CD4+CD25+调节性T淋巴细胞（Treg）相关细胞因子分泌水平的影响;Western Blot检测2组患者PPARα/γ信号通路相关蛋白表达。再将PBMC分为si-miRNA-18a抑制组（转染miRNA-18a抑制剂）和si-miRNA-18a正常对照组（转染miRNA-18a质粒）,用流式细胞技术检测抑制miRNA-18a表达对CD4+CD25+Treg细胞频率的影响,Western Blot检测2组P...
- 乙型肝炎,慢性 /
- 过氧化物酶体增殖物激活受体 /
- 微RNAs /
- T淋巴细胞,调节性
Abstract:
Objective To investigate the effect of microRNA-18 a(miRNA-18 a) on the regulatory immune function in patients withchronic hepatitis B(CHB) through the PPARα/γ signaling pathway.Methods A total of 98 CHB patients and 96 patients without hepatitisB, who were treated in Air Force Special Medical Center(formerly known as General Air Force Hospital, PLA) from April 2017 to October2018, were enrolled as experimental group and control group, respectively. There were no significant differences in age and sex between thetwo groups(P> 0. 05). RT-PCR was used to measure the relative mRNA expression of miRNA-18 a in serum; flow cytometry was usedto measure the expression of miRNA-18 a in peripheral blood mononuclear cells(PBMCs); ELISA was used to observe the effect of miRNA-18 a on the frequency of CD4+CD25+regulatory T(Treg) cells; Western blot was used to measure the expression of proteins associatedwith the PPARα/γ signaling pathway. PBMCs were further divided into si-miRNA-18 a inhibitor group(transfected with si-miRNA-18 a inhibitor) and si-miRNA-18 a normal control group(transfected with si-miRNA-18 a plasmid); flow cytometry was used to investi-gate the effect of miRNA-18 a inhibition on the frequency of CD4+CD25+Treg cells, and Western blot was used to measure the expressionof proteins associated with the PPARα/γ signaling pathway. Thet-test was used for comparison of normally distributed continuous data between two groups, and a Pearson correlation analysis was performed to investigate the correlation between miRNA-18 a expression and pro-teins associated with the PPARα/γ signaling pathway.Results Compared with the control group, the experimental group had significantlyupregulated mRNA expression of miRNA-18 a in serum and liver tissue(t= 9. 634 and 9. 863, bothP< 0. 01). The experimental grouphad a significantly higher frequency of CD4+CD25+Treg cells than the control group(t =9.854,P< 0. 01). Compared with the controlgroup, the experimental group had significantly upregulated levels of interferon-γ and interlukin-9(t =8. 235 and 8. 382, bothP<0. 05). Compared with the control group, the experimental group had significantly upregulated expression of PPARα and PPARγ （t =4. 229 and 3. 545, bothP< 0. 05). Compared with the si-miRNA-18 a normal control group, the si-miRNA-18 a inhibitor group had a signifi-cantly lower percentage of peripheral blood CD4+CD25+Treg cells among CD4+T cells(t =3.968,P< 0. 01). Compared with the si-miRNA-18 a normal control group, the si-miRNA-18 a inhibitor group had significantly lower expression of PPARα and PPARγ （t =5. 023 and 4. 983, bothP< 0. 05). miRNA-18 a was positively correlated with the protein expression of PPARα and PPARγ in thePPARα/γ signaling pathway(r= 0. 701 and 0. 682, bothP< 0. 05).Conclusion miRNA-18 a may affect the regulatory immune functionin CHB patients by activating the PPARα/γ signaling pathway and thus upregulate the frequency of cell surface factors and cytokine secretionlevels associated with immune function.
- hepatitis B,chronic /
- peroxisome proliferator-activated receptors /
- microRNAs /
- T-lymphocytes,regulatory

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参考文献(17)

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