急性冠脉综合征患者体内CD4^+CD25^+Foxp3^+调节性T细胞的变化及阿托伐他汀对其影响

Changes of naturally occurring CD4^+CD25^+Foxp3^+ Regulatory T cells in Patients with Acute Coronary Syndrome and the Effects of Atorvastatin

目的:研究急性冠脉综合征患者外周血CD4^+CD25^+Foxp3^+调节性T细胞的变化及阿托伐他汀对其影响。方法:经冠状动脉造影和血管内超声显示病变斑块狭窄率>50%或管腔面积<4 mm2临床诊断急性冠脉综合征患者120例,随机分成两组,即传统治疗组(主要使用行气活血,通脉止痛类中药)和传统治疗加阿托伐他汀治疗组,每组60例,选取健康人群48例作为对照组。比较各研究组外周血中CD4^+CD25^+Foxp3^+调节性T细胞的数目和功能;利用ELISA法检测各组细胞炎性因子浓度。结果:与传统治疗组比较,阿托伐他汀治疗组CD4^+CD25^+Foxp3^+调节性T细胞的数目显著增加(P<0.05),CD4^+CD25^+Foxp3^+调节性T细胞增殖反应下降;上清液中TGF-β和IL-10浓度显著升高,而IFN-γ浓度显著下降。结论:急性冠脉综合征患者循环血调节性T细胞数目及功能下降,阿托伐他汀治疗能增加CD4^+CD25^+Foxp3^+调节性T细胞数目并增强其功能,抑制急性冠脉综合征患者免疫炎性反应。

Objective Naturally occurring CD4^＋CD25^＋Foxp3^＋ regulatory T cells（n Tregs） exert suppressive effects on effector CD4 cells and downregulate experimental autoimmune disorders. We investigated the function of n Tregs in patients with acute coronary syndrome（ACS） and the effects of atorvastatin. Methods 120 patients with ACS were randomly divided into two groups. They were labelled as the conventional therapy group and the conventional therapy ＋ atorvastatin（20 mg/day,n = 60）group. T lymphocytes from ACS patients（before and 4 weeks after the treatment） and 48 healthy subjects were separated and flow cytometry was used detect the percentage of n Tregs. ELISA was used to measure the serum levels of cytokines（IL-10,TGF-β1,IFN-γ and hs CRP） before and after treatment. We used mixed lymphocyte reaction（MLR） to determine the inhibitory ability of n Tregs on effector T cells. Real-time quantitative RT-PCR and Western blot were used to analyse Foxp3 mRNA transcript levels and the expression of Foxp3 protein. Results The results showed that the tregs percentage was decreased significantly,the inhibitory ability of Tregs on the T lymphocytes proliferation was reduced,IFN-γ and hs CRP levels were increased and IL-10 and TGF-β1 levels were lowered in ACS patients,when compared with the normal control group. After treatment with atorvastatin,the treg percentage and the inhibitory ability of Tregs on T lymphocyte＇s proliferation were significantly increased in ACS patients. Serum IFN-γ and hs CRP was decreased significantly,while IL-10 and TGF-β1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-β1 and IL-10,but negatively correlated with serum IFN-γ and CRP. Conclusions This study provides prospective evidence for the role of n Tregs in the progression of atherosclerosis. The findings are in accordance with previous experimental studies and provide clinical support for a protective role of n Tregs in atherosclerosis. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on n Tregs and restoration of immune homeostasis.