2型固有淋巴细胞在糖尿病肾脏疾病发病机制中作用的研究

The role of type 2 innate lymphocytes in the pathogenesis of diabetic kidney disease

目的探讨2型固有淋巴细胞(ILC2s)在DKD发病机制中的作用。方法选取2017年8月至2018年1月于西南医科大学附属医院内分泌科住院的T2DM患者30例,DKD患者30例,另选取同期体检中心健康志愿者30名,分为T2DM组(n=30)、早期DKD组(DKD1,n=15)或晚期DKD组(DKD2,n=15)及正常对照组(NC,n=30)。流式细胞术和ELISA法检测各组血液中ILC2s比例和IL-4、IL-13水平。分别用IL-4或IL-13单独或联合高糖干预人肾小管上皮细胞(HK-2),ELISA和qPCR检测其转化生长因子β1(TGF-β1)和纤连蛋白(FN)表达水平。结果与NC组比较,T2DM、DKD1、DKD2组外周血ILC2s比例、IL-4、IL-13水平升高,DKD2组高于DKD组(P<0.05)。HK-2细胞培养、分组干预后,与Con组比较,其他组TGF-β1、FN及mRNA表达均升高(P<0.05);与IL-4组比较,HG+IL-4组TGF-β1、FN及mRNA表达均升高(P<0.05);与IL-13组比较,HG+IL-13组TGF-β1、FN及mRNA表达均升高(P<0.05)。结论 ILC2s可能部分通过分泌2类细胞因子促进DKD肾纤维化发展。

Objective To investigate the role of type 2 innate lymphocytes(ILC2s)in the pathogenesis in diabetic kidney disease(DKD).Methods The peripheral fasting blood of patients with type 2 diabetes mellitus(T2DM),early or advanced DKD and healthy volunteers were collected,30 cases in each group.The proportion of ILC2 s and the levels of IL-4 and IL-13 were detected by ELISA or flow cytometry.Renal tubular epithelial cells(HK-2)cultured in normal or high glucose were intervened with IL-4 or IL-13.The expression and release of transforming growth factor-β1(TGF-β1)and fibronectin(FN)were detected.Results Compared with the NC group,the proportion of ILC2 s and the levels of IL-4 and IL-13 in peripheral blood of T2DM group,DKD1 group and DKD2 group were increased,and the proportion of ILC2s and the levels of IL-4 and IL-13 were the highest in DKD2 group(P<0.05).Compared with the Con group,the expressions of TGF-β1,FN and m RNA in the other groups were increased(P<0.05).When compared with the IL-4 group,the expressions of TGF-β1,FN and m RNA in the HG+IL-4 group were increased(P<0.05).Compared with the IL-13 group,the expressions of TGF-β1,FN and m RNA in the HG+IL-13 group were all increased(P<0.05).Conclusion ILC2s may promote the development and progression of DKD by secreting Th2 cytokines and promoting renal fibrosis.