骨化三醇对局灶增生性IgA肾病患者CD4＋记忆性T细胞的影响  

Effects of 1α, 25-dihydroxyvitamin D3 on memory CD4＋ T cells of focal proliferative IgA nephropathy

作　　者：于春洋[1] 罗静[2] 李荣山[3] 王利华[1] 郭珲[1] 

机构地区：[1]山西医科大学第二医院肾内科山西省肾脏病研究所,太原030001 [2] 山西医科大学第二医院风湿科,太原030001 [3] 山西省人民医院肾内科山西省肾脏病研究所

出　　处：《中华肾脏病杂志》2014年第7期486-493,共8页Chinese Journal of Nephrology

基　　金：山西省国际科技合作项目（2013081056）;山西省回国留学人员科研资助项目（2013-117）;山西省科技攻关项目（20130313022-3）

摘　　要：目的 探讨骨化三醇[1,25（OH）2D3]对局灶增生性IgA肾病（IgAN）患者外周血CD4＋记忆性T细胞的影响.方法 选取局灶增生性IgAN患者（Lee Ⅲ级）20例（IgAN组）及健康志愿者20例（健康对照组）为研究对象.IgAN组再分为尿蛋白量＜1g/24h和尿蛋白量≥1g/24 h两亚组.用放射免疫测定法（RIA）检测血清1,25（OH）2D3水平;采用Ficoll密度梯度离心法分离外周血单个核细胞（PBMCs）,分别给予不同浓度的1,25（OH）2D3、地塞米松（DEX）或者2种药物联合处理PBMCs,细胞培养72 h后用流式细胞仪检测人干扰素（IFN）-γ、白细胞介素（IL）-4、IL-17A、人叉头框蛋白P3 （human forkhead box P3,Foxp3）的变化.结果 与健康对照组相比,IgAN组患者血清1,25（OH）2D3水平显著降低（P＜0.05）;与尿蛋白量＜1 g/24 h亚组及健康对照组比较,尿蛋白量≥1 g/24 h亚组患者血清1,25（OH）2D3水平明显降低（均P＜0.05）.与健康对照组相比,IgAN组患者PBMCs分泌IFN-y、IL-17A水平及IFN-γ/IL-4、IL-17A/Foxp3比值明显升高,Foxp3水平明显降低（均P＜0.05）;与尿蛋白量＜1 g/24h亚组及健康对照组比较,尿蛋白量≥1 g/24 h亚组PBMCs分泌IFN-γ、IL-17A水平及IL-17A/Foxp3比值明显升高,Foxp3水平明显降低,IFN-γ/IL-4比值升高（均P＜0.05）.1,25（OH）2D3处理后,PBMCs分泌IFN-γ、IL-17A、IFN-γ/IL-4、IL-17 A/Foxp3水平明显降低,Foxp3水平明显升高,并呈剂量依赖关系（均P＜ 0.05）;1,25 （OH）2D3＋DEX联合刺激PBMCs后,上述IFN-y、IL-17A、IFN-γ/IL-4、IL-17A/Foxp3、Foxp3变化更加显著,且IL-4水平明显降低（均P＜0.05）.结论 局灶增生性IgAN患者存在维生素D缺乏,并与蛋白尿的严重程度相关;局灶增生性IgAN患者可能存在CD4＋记忆性T细胞功能紊乱,1,25（OH）2D3具有纠正局灶增生性IgAN患者CD4＋记忆性T细胞功能紊乱的作用.Objective To explore the effects of 1α,25-dihydroxyvitamin D3 [1,25（OH）2D3] on memory CD4＋T cells of focal proliferative IgA nephropathy （IgAN）patients.Methods （1） Total of twenty incipient focal proliferative IgAN patients （Lee classification：Ⅲ level） were chosen as IgAN group and 20 healthy volunteers were chosen as healthy control group.The level of serum 1,25（OH）2D3 was measured by radioimmunoassay （RIA）.Peripheral blood mononuclear cells （PBMCs） were separated by the method of Ficoll density gradient centrifugation and were stimulated with anti-CD3/anti-CD28 in the absence or presence of various concentrations of 1,25（OH）2D3,Dexamethasone（DEX） and 1,25（OH）2D3and DEX combined.PBMCs were cultured for 72 hours and the levels of IFN-γ,IL-4,IL-17A,Foxp3 were measured by flow cytometry（FCM）,standing for the levels of Th1,Th2,Th17,Treg.（2） IgAN group was divided into two subgroups （proteinuria 〈 1 g/24 h subgroup,proteinuria≥ 1 g/24 h subgroup）,then the serum levels of 1,25（OH）2D3,IFN-γ,IL-4,IL-17A,Foxp3 were compared.Results Compared with healthy control group,serum 1,25（OH）2D3 level of IgAN group was significantly lower （P 〈 0.05）.Serum 1,25（OH）2D3 level in proteinuria≥ 1 g/24 h subgroup was significantly lower than proteinuria 〈 1 g/24 h subgroup and healthy control group （P 〈 0.05）.The level in proteinuria 〈 1 g/24 h subgroup was lower than healthy control group,but the difference was not statistically significant （P 〉 0.05）.（2） The levels of IFN-γ and IL-17A and the ratios of IFN-γ/IL-4,IL-17A/Foxp3 in IgAN group increased significantly compared with healthy control group （all P 〈 0.05）,and the level of Foxp3 decreased significantly （P 〈 0.05）.The level of IL-4 also increased,but the difference was not statistically significant （P 〉 0.05）.The levels of IFN-γand IL-17A and the ratio of IL-17A/Foxp3 in proteinuria≥ 1 g/24 h subgroup increased significantly,and the level of Foxp3 decreas

关 键 词：骨化三醇 CD4阳性T淋巴细胞 蛋白尿 

分 类 号：R692.31[医药卫生—泌尿科学]