阿托伐他汀对不稳定型心绞痛患者树突状细胞功能的影响

Effects of atorvastatin on the function of dendritic cells in patients with unstable angina pectoris

目的 研究不稳定型心绞痛患者 (UAP)树突状细胞 (DC)的功能及阿托伐他汀对其的影响。方法 将 2 7例UAP分为常规治疗组 (12例 )和常规加阿托伐他汀治疗组 (15例 ) ,分别于治疗前及治疗后 2周取血分离外周血单个核细胞 ,在含粒细胞巨噬细胞集落刺激因子和白细胞介素 (IL) 4的培养条件下制备DC。用流式细胞仪检测DC表面共刺激分子CD86(B7 2 )的表达 ;混合淋巴细胞反应(MLR)检测DC对同种异体T淋巴细胞的刺激能力 ;ELISA法测定MLR上清液中的细胞因子 ;探讨CD86表达与冠心病危险因素及C反应蛋白 (CRP)的相关性。结果 与正常对照组比较 ,UAP者DC表面CD86的表达明显增高 ;对T淋巴细胞刺激的能力增强 ;经DC刺激的淋巴细胞分泌致炎细胞因子(IL 1β ,IL 6 ,肿瘤坏死因子α)增多 ,抑炎细胞因子 (IL 10 )减少 ;用药前CD86的表达与血LDL C水平正相关 ;阿托伐他汀抑制DC功能的同时显著降低血CRP水平 ;且CD86与CRP水平正相关。结论 (1)UAP者DC的功能亢进 ,由此启动的T淋巴细胞的增殖和炎性细胞因子分泌可能是UAP者动脉斑块不稳定的原因 ,(2 )LDL C可能是其刺激因素 ;(3)阿托伐他汀抑制斑块炎症的机制之一是其对DC的抑制。

Objective To investigate the function of dendritic cells (DC) in patients with unstable angina pectoris (UAP) and the effects of atorvastatin on it. Methods 27 patients with UAP were divided into two groups treated respectively with regular pharmacotherapy and regular pharmacotherapy plus atorvastatin. PBMC from the UAP patients(before and 2 weeks after the treatment) and 11 healthy subjects were incubated and induced to mature DC in a completed medium containing GM-CSF and IL-4. Flow cytometric analysis was used to detect the expression of co-stimulating factor CD86(B7-2)on DC. The stimulating capacity of DC was determined in allogenic mixed lymphocyte reaction (MLR).ELISA was used to analyze the level of cytokines(IL-1β,IL-6,IL-10 and TNF-α) in the medium of MLR. Relationship of expression of CD86 to risk factors and blood CRP level was also analyzed. Results When compared with normal group,CD86 on DC was much more expressed in UAP patinets;the stimulating capacity of DC in MLR was higher ; T lymphocytes in MLR secreted higher levels of pro-inflammation cytokines(IL-1β,IL-6 and TNF-α) and lower level of anti-inflammation cytokine (IL-10). Blood LDL-C before treatment was positively related to the expression of CD86. Atorvastatin inhibited the function of DC and lowered blood level of CRP and CD86,the levels of which were significantly positively correlated. Conclusions DC in UAP are activated,which may play an important role in initiating immune reaction in the plaque. LDL-C may be one of the activators of DC;inhibitory effect of atorvastatin on inflammation in UAP may be due to its inhibition on DC.