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

RelationshipbetweenILC2sandmetabolicsyndromeinhemodialysispatientswithdiabeticnephropathy

摘要:

目的：探讨Ⅱ型固有淋巴细胞（groupⅡinnatelymphoidcells，ILC2s）与糖尿病肾病血液透析患者机体内代谢综合征（metabolicsyndrome，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（peripheralbloodmononuclearcells，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（?字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。

Abstract:

Objective：Toinvestigatetherelationshipbetweentype2innatelymphoidcells（ILC2s）andmetabolicsyndrome（MS）inhemodialysispatientswithdiabeticnephropathy（DN）.Methods：Atotalof105hemodialysispatientsinourhospitalwereenrolledinthisstudy，including40DNpatients（hemodialysis+DNgroup）and65patientswithnon-diabeticnephropathy（hemodialysis+NDNgroup）.Theclinicaldatawerecollected.Anthropometricparameters，bloodglucose，andbloodlipidsweremeasured.And35patientswithtype2diabetesalone（diabetesgroup）and30outpatientsreceivingphysicalexamination（healthycontrolgroup）wereselectedascontrol.ThemRNAexpressionlevelsofILC2srelatedfactorsinperipheralbloodmononuclearcellsweredeterminedbyquantitativereal-timePCR.ILC2s%wasmeasuredbyflowcytometry.TheproteinexpressionlevelsofILC2srelatedcytokines（interleukin[IL]-5andIL-13）inplasmaweremeasuredbyenzyme-linkedimmunosorbentassay.Results：Thehemodialysis+DNgrouphadasignificant－lyhigherincidencerateofMScomparedwiththehealthycon－trolgroup，thediabetesgroup，andthehemodialysis+NDNgroup（87.5%vs.0%，57.10%，and50.80%，?字2=53.084，P=0.000）.Com－paredwiththehealthycontrolgroup，thehemodialysis+DNgrouphadsignificantlyhighermRNAexpressionlevelsofILC2schar－acteristictranscriptionfactorROR-alpha，membranereceptorT1/ST2，IL-17B，IL-5，andIL-13（P=0.000，P=0.000，P=0.000，P=0.000，P=0.004）andhadsignificantlyhigherproteinexpressionlev－elsofIL-5andIL-13（P=0.012，P=0.076）.Theflowcytometryresultsshowedthatthehemodialysis+DNgrouphadasignificantlyhigherILC2s%thantheotherthreegroups（F=185.287，P=0.000）.LogisticregressionanalysisshowedthatwiththeincreasingILC2sactivity，thehemodialysis+DNgrouphadahigherprobabilityofMSthantheotherthreegroups.CorrelationanalysisindicatedthatILC2swaspositivelycorrelatedwithwaistcircumferenceandtriglyceridelevelinhemodialysispatientswithDN（r=0.356，P=0.024；r=0.462，P=0.003）.Conclusion：HemodialysispatientswithDNhaveahigherprevalenceofMS.ILC2sappearstobethedominantactivationstateinhemodialysispatientswithDN.ILC2srelatedfactorsmaybeinvolvedintheformationofMSinhemodialysispatientswithDNthroughtheeffectsonabdominalobesityandlipidmetabolism.