原发性膜性肾病患者外周血SOCS1/SOCS3表达及与Th17/Treg细胞平衡的关系

Expression of SOCS1/SOCS3 in Peripheral Blood of Patients with Primary Membranous Nephropathy and its Relationship with Th17/Treg Cell Balance

目的:检测原发性膜性肾病(PMN)患者外周血中细胞因子信号转导蛋白抑制因子1/3(SOCS1/SOCS3)的表达情况及辅助性T细胞17/调节性T细胞(Th17/Treg),探讨SOCS1/SOCS3与Th17/Treg的关系。方法:选取2017年09月~2019年11月在本院接收的PMN患者(PMN组)103例,根据疾病危险程度分为低危组(24例)、中危组(27例)、高危组(29例)和重危组(23例),选取同期健康体检者100例作为对照。分别采集PMN患者和健康体检者外周血并分离出血清,利用酶联免疫吸附法(ELISA)检测外周血血清SOCS1、SOCS3、白细胞介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)表达水平,利用流式细胞仪检测外周血Th17细胞和Treg细胞水平并计算比值。采用Pearson法分析PMN患者SOCS1、SOCS3水平与IL-17、TNF-α、TGF-β1、Th17/Treg水平的相关性和Th17/Treg与IL-17、TNF-α、TGF-β1的相关性。结果:与对照组相比,PMN组患者外周血SOCS1、SOCS3、IL-17、TNF-α和Th17/Treg水平均明显升高,TGF-β1水平明显降低(P<0.05);随着疾病危险程度的加重,PMN患者外周血SOCS1、SOCS3、IL-17、TNF-α和Th17/Treg水平均明显升高,TGF-β1水平明显降低(P<0.05);PMN患者外周血SOCS1、SOCS3、Th17/Treg水平与IL-17、TNF-α均明显正相关,与TGF-β1均明显负相关(P<0.05);PMN患者外周血SOCS1、SOCS3与Th17/Treg均明显正相关(P<0.05)。结论:随着疾病的发生及加重,PMN患者外周血SOCS1、SOCS3、IL-17、TNF-α和Th17/Treg水平均明显上调,TGF-β1水平明显下调,且SOCS1、SOCS3可能通过上调IL-17、TNF-α水平,下调TGF-β1水平,使得Th17/Treg细胞失衡从而影响疾病。

Objective:To detect the expression of cytokine signal transduction protein inhibitor 1/3(SOCS1/SOCS3)and helper T cell 17/regulatory T cell(Th17/Treg)in peripheral blood of patients with primary membranous nephropathy(PMN),and to explore the relationship between SOCS1/SOCS3 and Th17/Treg.Methods:103 PMN patients(PMN group)received in our hospital from September 2017 to November 2019 were divided into low-risk group(24 cases),medium-risk group(27 cases),high-risk group(29 cases)and critical group(23 cases)according to the degree of disease risk.100 healthy persons in the same period were selected as the control group.Peripheral blood samples were collected from PMN patients and healthy persons,and the hemorrhagic serum was separated.The expression levels of SOCS1,SOCS3,interleukin-17(IL-17),tumor necrosis factor-α(TNF-α)and transforming growth factor-β1(TGF-β1)in peripheral blood were detected by enzyme-linked immunosorbent assay(ELISA),the levels of Th17 cells and Treg cells in peripheral blood were measured by flow cytometry and the ratio was calculated.Pearson method was used to analyze the correlations between SOCS1,SOCS3 levels and IL-17,TNF-α,TGF-β1,Th17/Treg levels in PMN patients,and the correlations between Th17/Treg and IL-17,TNF-α,TGF-β1.Results:Compared with the control group,the levels of SOCS1,SOCS3,IL-17,TNF-αand Th17/Treg in peripheral blood of PMN group were significantly higher,while the level of TGF-β1 was significantly lower(P<0.05).With the increase of disease risk,the levels of SOCS1,SOCS3,IL-17,TNF-αand Th17/Treg in peripheral blood of PMN patients increased significantly,while the level of TGF-β1 decreased significantly(P<0.05).The levels of SOCS1,SOCS3 and Th17/Treg in peripheral blood of PMN patients were positively correlated with IL-17 and TNF-α,and negatively correlated with TGF-β1(P<0.05).SOCS1 and SOCS3 in peripheral blood of PMN patients were positively correlated with Th17/Treg(P<0.05).Conclusion:With the occurrence and aggravation of the disease,the levels of SOCS1,SOCS3,IL-17,TNF-αand Th17/Treg in peripheral blood of PMN patients are significantly increased,and the level of TGF-β1 is significantly decreased.SOCS1 and SOCS3 may cause the imbalance of Th17/Treg cells and affect the disease by up-regulating the levels of IL-17 and TNF-αand down-regulating the levels of TGF-β1.