过敏性哮喘患者外周血SOCS-1、SOCS-3表达及与Th17/Treg失衡的关系

Expression of SOCS-1 and SOCS-3 in peripheral blood of patients with allergic asthma and their relationship with imbalance of Th17/Treg

目的检测过敏性哮喘患者外周血单个核细胞细胞因子信号传导抑制蛋白1(SOCS-1)、SOCS-3表达水平并分析其与Th17/Treg失衡的关系及意义。方法选取2018年4月—2019年9月四川省遂宁市中心医院急诊科诊治过敏性哮喘患者60例为哮喘组,另选取同期于医院进行体检的健康体检者60例作为健康对照组,采用实时荧光定量PCR(qRT-PCR)检测2组外周血单个核细胞SOCS-1、SOCS-3 mRNA表达水平,流式细胞仪检测外周血CD4+IL-17+T细胞(Th17细胞)、CD4+CD25+调节性T细胞(Treg细胞)百分率,采用酶联免疫吸附法(ELISA)检测血清IL-6、IL-17、IL-23、TGF-β1、IFN-γ水平,Pearson相关分析过敏性哮喘患者Th17/Treg比值与SOCS-1、SOCS-3 mRNA表达水平相关性。结果哮喘组外周血Th17细胞百分率、Th17/Treg比值显著高于健康对照组,Treg细胞百分率显著低于健康对照组(t=15.726、2.665、15.074,P均<0.01);哮喘组外周血单个核细胞SOCS-1、SOCS-3 mRNA表达水平较健康对照组显著上调(t=10.805、4.709,P均=0.000);与健康对照组比较,哮喘组患者血清IL-6、IL-17、IL-23、TGF-β1表达水平显著升高,IFN-γ表达水平显著降低(t=26.648、11.963、6.844、58.921、8.900,P均=0.000);哮喘组患者FEV1、FVC、FEV1%显著低于健康对照组(t=12.316、6.142、35.372,P均=0.000);过敏性哮喘患者外周血SOCS-1、SOCS-3 mRNA表达水平与IL-6、IL-17、IL-23、TGF-β1水平均呈正相关(SOCS-1:r=0.576、0.365、0.525、0.478,P均<0.01;SOCS-3:r=0.463、0.427、0.364、0.415,P均<0.01),与IFN-γ水平均呈负相关(r=-0.549、-0.562,P均<0.01),SOCS-3 mRNA水平与SOCS-1 mRNA水平呈正相关(r=0.471,P<0.01);SOCS-1、SOCS-3 mRNA与Th17/Treg比值呈正相关(r=0.488、0.606,P均<0.05)。结论过敏性哮喘患者外周血SOCS-1、SOCS-3表达上调,与Th17/Treg失衡及炎性因子异常表达有关,可能参与过敏性哮喘发生。

Objective To detect the expression level of monocyte cytokine signal transduction inhibitory protein 1(SOCS-1)and SOCS-3 in peripheral blood of patients with allergic asthma,and analyze the relationship and significance between them and Th17/Treg imbalance.Methods From April 2018 to September 2019,60 patients with allergic asthma were selected as asthma group.In addition,60 healthy people who had physical examination in the hospital at the same time were selected as the control group.The expression of SOCS-1 and SOCS-3 mRNA in peripheral blood mononuclear cells of the two groups was detected by real-time fluorescent quantitative PCR(qRT-PCR).The percentage of CD4+IL-17+T cells(Th17 cells)and CD4+CD25+regulatory T cells(Treg cells)in peripheral blood were detected by flow cytometry.The serum levels of IL-6,IL-17,IL-23,TGF-β1 and IFN-γwere detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation analysis showed that Th17/Treg ratio was related to the expression level of SOCS-1 and SOCS-3 mRNA in patients with allergic asthma.Results The percentage of Th17 cells and the ratio of Th17/Treg in peripheral blood of asthma group were significantly higher than that of healthy control group,and the percentage of Treg cells was significantly lower than that of healthy control group(t=15.726,2.665,15.074,P<0.01).The expression level of SOCS-1 and SOCS-3 mRNA in peripheral blood mononuclear cells of asthma group was significantly higher than that of healthy control group(t=10.805,4.709,P=0.000).Compared with the healthy control group,the levels of serum IL-6,IL-17,IL-23,TGF-β1 in the asthma group were significantly higher,and the levels of IFN-γwere significantly lower(t=26.648,11.963,6.844,58.921,8.900,P=0.000);FEV1,FVC,FEV1%in the asthma group were significantly lower than those in the healthy control group(t=12.316,6.142,35.372,P=0.000).The expression of SOCS-1 and SOCS-3 mRNA was positively correlated with the levels of IL-6,IL-17,IL-23 and TGF-β1(SOCS-1:r=0.576,0.365,0.525,0.478,P<0.01;SOCS-3:r=0.463,0.427,0.364,0.415,P<0.01),and negatively correlated with IFN-γ(r=-0.549,-0.562,P<0.01),respectively mRNA level was positively correlated(r=0.471,P<0.01).There was a positive correlation between SOCS-1,SOCS-3 mRNA and Th17/Treg ratio(r=0.488,0.606,P<0.05).Conclusions The up-regulated expression of SOCS-1 and SOCS-3 in the peripheral blood of patients with allergic asthma is related to the imbalance of Th17/Treg and the abnormal expression of inflammatory factors,which may be involved in the occurrence of allergic asthma.