二甲双胍对HIV-1感染者免疫细胞功能影响的研究  

The effect of metformin on immune cell function in HIV-1 infected patients

作　　者：刘夫华 吴逢英 代晓朋 夏鹏 赵金芳 张纪元 王福生 LIU Fuhua;WU Fengying;DAI Xiaopeng;XIA Peng;ZHAO jinfang;ZHANG Jiyuan;WANG Fusheng(Savaid Medical School,University of Chinese Academy of Sciences,Beijing 100049,China;Treatment and Research Center for Infectious Diseases,The Fifth Medical Center of PLA General Hospital,Beijing 100039;Office of Medical Laboratory Technology,Department of Medical Technology Support,Sergeant school of Third Military Medical University,Shijiazhuang 050081)

机构地区：[1]中国科学院大学存济医学院,北京100049 [2]中国人民解放军总医院第五医学中心国家感染性疾病临床医学研究中心,北京100039 [3]中国人民解放军陆军军医大学士官学校医技保障系医学检验技术教研室,石家庄050081

出　　处：《中国艾滋病性病》2021年第6期570-576,共7页Chinese Journal of Aids & STD

基　　金：北京大学临床科学家专项、中央高校基本科研业务费专项资金资助(BMU2019LCKXJ013);传染病重大专项(2018ZX10302104-003)。

摘　　要：目的体外实验探究二甲双胍对HIV-1感染者CD8细胞功能、CD4细胞的存活和单核细胞释放促炎性因子的作用。方法选取未接受抗病毒治疗的HIV-1感染者为研究对象,将健康受试者作为对照,二甲双胍和不同刺激剂组合活化刺激两组受试者的PBMCs,采用流式细胞技术检测二甲双胍对CD8细胞、CD4细胞和单核细胞的作用。结果二甲双胍显著促进HIV-1特异性CD8细胞分泌IFN-γ,并在800μM浓度达到峰值(平均值3.28%vs.1.0%)。使用HIV-1肽库刺激,二甲双胍促进CD8细胞分泌IFN-γ的作用与在CD3/CD28抗体活化体系中结果相似。此外,二甲双胍明显降低尼日利亚菌素(nigericin)诱导的CD4细胞caspase-1的表达水平,50μM浓度下,HIV-1感染者CD4细胞caspase-1表达量降低6.7%(平均值22.7%vs.29.4%)。在脂多糖(LPS)诱导的单核细胞中,10000μM浓度下,TNF-α表达降低10.8%(平均值37.7%vs.48.5%),IL-6表达降低10.5%(平均值62.5%vs.73.0%)(P<0.05),并且具有浓度梯度效应。结论二甲双胍在体外能显著增强CD8细胞HIV-1特异性反应,促进CD4细胞存活,并有效降低单核细胞释放促炎性细胞因子。Objective To explore the effects of metformin on CD8+T cell function,CD4+T cell survival,and the release of inflammatory cytokines from monocytes in human immunodeficiency virus(HIV-1)infected patients in vitro.Methods We selected HIV-1-infected patients who did not receive combined antiretroviral therapy(cART)as the research subjects.Healthy people were used as controls.A combination of metformin and different activators stimulated the peripheral blood mononuclear cells(PBMCs)of the two groups of subjects.Flow cytometry was used to detect the effects of metformin on CD8+T cells,CD4+T cells,and monocytes.Results Metformin significantly promoted the secretion of IFN-γfrom HIV-1-specific CD8+T cells and reached a peak at a concentration of 800μM(mean 3.28%vs1.0%).After using HIV-1 gag peptide as stimulation,the effect of metformin in promoting the secretion of IFN-γfrom CD8+T cells is similar to that in the CD3/CD28 antibody activation system.In addition,metformin significantly reduced the level of caspase-1 in CD4+T cells induced by nigericin.The expression of caspase-1 in CD4+T cells of HIV-1 infected patients was decreased by 6.7%(mean 22.7%vs 29.4%)at the concentration of 50μM.The expression of TNF-αwas decreased by 10.8%(mean 37.7%vs 48.5%),and the IL-6 expression was decreased by 10.5%(mean 62.5%vs 73.0%)(P<0.05)at the concentration of 10,000μM in LPSinduced monocytes.The effect is concentrationdependent.Conclusion Metformin can significantly enhance the HIV-1 specific response of CD8+T cells in vitro,promote the survival of CD4+T cells,and effectively reduce the release of inflammatory cytokines from monocytes.

关 键 词：二甲双胍 1型艾滋病病毒 CD8细胞 CD4细胞 单核细胞 

分 类 号：R373.9[医药卫生—病原生物学]