抑郁症首次发病患者内皮祖细胞数量和功能变化的初步研究

The change of peripheral blood endothelial progenitor cells in patients with newly diagnosed depression

目的 探讨抑郁症首次发病患者外周血内皮祖细胞（endothelial progenitor cells,EPCs）数量和功能的变化及其与血压、血糖、血脂、炎症因子等各因素的关系.方法 选择符合《中国精神疾病分类与诊断标准（第3版）》抑郁症诊断标准,且24项汉密尔顿抑郁量表（HAMD24）评分≥21分的抑郁症首次发病患者30例（患者组）及年龄和性别匹配的健康志愿者（对照组）30名.采用HAMD24评定抑郁症状严重程度,使用流式细胞检测仪检测外周血循环EPCs数量,采用Ficoll密度梯度离心法分离培养外周血单个核细胞,采用MTT比色法检测细胞增殖功能,采用酶标化学发光免疫法检测血清白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平,采用免疫透射比浊法检测血清超敏C反应蛋白（hs-CRP）水平；采用Spearman相关分析评价IL-6、TNF-α、hs-CRP水平与循环EPCs数量的关系,采用多元线性回归分析评价一般临床资料和HAMD评分与循环EPCs数量的关系.结果 （1）患者组外周血EPCs CD34＋ CD133＋ KDR＋细胞数量[（13.32±5.65） ×103个/L]和细胞增殖率[（0.44±0.04）％]低于对照组[（24.39±9.94）×103个/L、（0.61±0.05）％],血清IL-6水平[（8.76±3.18） ng/L]和TNF-α水平[（14.95 ±5.54） ng/L]高于对照组[（3.11±3.18）、（4.67±2.23） ng/L],差异均有统计学意义（t=-6.69、-14.23、5.31、4.22,均P＜0.05）；（2） Spearman相关分析显示,患者组IL-6（r=-0.441、-0.529）和TNF-α水平（r=-0.433、-0.313）与循环EPCs的数量和增殖率呈负相关（均P ＜0.05）；（3）多元线性逐步回归分析显示,HAMD总分和IL-6水平是循环EPCs数量的独立影响因素（均P＜0.05）.结论 抑郁症首次发病患者EPCs数量减少、功能减退,HAMD总分及IL-6水平是循环EPCs的独立影响因素.

Objective To detect the number and function changes of endothelial progenitor cells （EPCs） from peripheral blood in patients with first-episode depression and explore their correlation with blood pressure,glucose,lipids,inflammation.Methods The study included thirty first-episode depression patients and 30 healthy controls.The Hamilton Depression Rating Scale-24 （HAMD24） was used to assess the severity of depression.Peripheral blood EPCs were counted by flow cytometry.Mononuclear cells （MNCs） was isolated from peripheral blood by ficoll density-gradients centrifugation.After 7 days of culture,EPC proliferation activity was determined by MTT assay.The plasma levels of tumor necrosis factor （TNF）-α and interleukin （IL）-6 were assayed by using enzyme-labeled chemiluminescent sequential immunometric assay.Additionally,the high-sensitive C-reactive protein （hs-CRP） was detected by turbidimetric immunoassay.Results （1） Number and function activity of EPCs in patients were significantly lower than the controls [（13.32 ± 5.65） × 103 vs.（24.39 ± 9.94） × 103,（0.44 ± 0.04） % vs.（0.61 ±0.05） %,t =-6.69,-14.23,P 〈 0.05].（2） Significant increase was observed in serum IL-6 and TNF-α level in patients [（8.76 ± 3.18）,（14.95 ± 5.54） ng/L] compared with controls [（3.11 ± 3.18）,（4.67 ±2.23） ng/L,t =5.31,4.22,P 〈0.05] and these had negative correlation with the number and proliferation activity of EPCs.（3） By multiple linear stepwise regression analysis,HAMD and IL-6 were the independent factors affecting EPCs number （P 〈 0.05）.Conclusions The number and proliferation activity of EPCs are probably decreased in patients with first-episode depression,and neovascularization and repairment of damaged endothelium may be impaired in these patients,which could increase risk of coronary heart disease.