ILC2s与糖尿病肾病血液透析患者机体内“代谢综合征”状态的关系研究

Relationship between ILC2s and metabolic syndrome in hemodialysis patients with diabetic nephropathy

目的:探讨Ⅱ型固有淋巴细胞(groupⅡinnate lymphoid cells,ILC2s)与糖尿病肾病血液透析患者机体内代谢综合征(metabolic syndrome,MS)状态的关系。方法:对江苏大学附属人民医院105例血液透析患者进行研究,其中糖尿病肾病40例,非糖尿病肾病65例,收集临床资料,进行人体指标测量,血糖、血脂指标测定,以同期单纯2型糖尿病患者35例、门诊健康体检者30例作为对照。实时荧光定量PCR检测外周血单个核细胞(peripheral blood mononuclear cells,PBMC)中ILC2s相关因子的mRNA表达水平;流式细胞术检测ILC2s的百分比;ELISA法检测血浆ILC2s相关细胞因子IL-5和IL-13的蛋白表达水平。结果:糖尿病肾病血透组患者MS的患病率为87.5%,较健康对照组(0%),2型糖尿病组(57.10%)和非糖尿病肾病血透组(50.80%)明显升高(χ^2=53.084,P=0.000);ILC2s特征性转录因子RORα,膜受体T1/ST2、IL-17B,细胞因子IL-5、IL-13的mRNA表达水平均较健康对照组升高(P=0.000,P=0.000,P=0.000,P=0.000,P=0.004),ILC2s相关细胞因子IL-5、IL-13的蛋白表达水平均较健康对照组升高(P=0.012,P=0.076);流式细胞术检测的ILC2s%较其余3组升高(F=185.287,P=0.000);logistic回归分析发现伴随ILC2s活性增强,糖尿病肾病血透组患者存在代谢综合征的概率较其余3组增加,相关性分析提示ILC2s与糖尿病肾病血液透析患者腰围和甘油三酯水平呈正相关(r=0.356,r=0.462;P=0.024,P=0.003)。结论:糖尿病肾病血液透析患者有较高的MS患病率,ILC2s在糖尿病肾病血液透析患者机体内表现为优势活化状态,ILC2s相关因子可能通过对腹型肥胖、脂质代谢的影响,而参与糖尿肾病血液透析患者MS状态的形成。

Objective:To investigate the relationship between type 2 innate lymphoid cells(ILC2s)and metabolic syndrome(MS)in hemodialysis patients with diabetic nephropathy(DN).Methods:A total of 105 hemodialysis patients in our hospital were enrolled in this study,including 40 DN patients(hemodialysis+DN group)and 65 patients with non-diabetic nephropathy(hemodialysis+NDN group).The clinical data were collected.Anthropometric parameters,blood glucose,and blood lipids were measured.And 35 patients with type 2 diabetes alone(diabetes group)and 30 outpatients receiving physical examination(healthy control group)were selected as control.The mRNA expression levels of ILC2s related factors in peripheral blood mononuclear cells were determined by quantitative real-time PCR.ILC2s%was measured by flow cytometry.The protein expression levels of ILC2s related cytokines(interleukin[IL]-5 and IL-13)in plasma were measured by enzyme-linked immunosorbent assay.Results:The hemodialysis+DN group had a significantly higher incidence rate of MS compared with the healthy control group,the diabetes group,and the hemodialysis+NDN group(87.5%vs.0%,57.10%,and 50.80%,χ^2=53.084,P=0.000).Compared with the healthy control group,the hemodialysis+DN group had significantly higher mRNA expression levels of ILC2s characteristic transcription factor ROR-alpha,membrane receptor T1/ST2,IL-17B,IL-5,and IL-13(P=0.000,P=0.000,P=0.000,P=0.000,P=0.004)and had significantly higher protein expression levels of IL-5 and IL-13(P=0.012,P=0.076).The flow cytometry results showed that the hemodialysis+DN group had a significantly higher ILC2s%than the other three groups(F=185.287,P=0.000).Logistic regression analysis showed that with the increasing ILC2s activity,the hemodialysis+DN group had a higher probability of MS than the other three groups.Correlation analysis indicated that ILC2s was positively correlated with waist circumference and triglyceride level in hemodialysis patients with DN(r=0.356,P=0.024;r=0.462,P=0.003).Conclusion:Hemodialysis patients with DN have a higher prevalence of MS.ILC2s appears to be the dominant activation state in hemodialysis patients with DN.ILC2s related factors may be involved in the formation of MS in hemodialysis patients with DN through the effects on abdominal obesity and lipid metabolism.