【摘要】 目的:观察普伐他汀对急性冠状动脉综合征(ACS)患者外周血单核细胞(PBMC)在一定浓度的C反应蛋白(CRP)诱导下IL-6基因表达与分泌的影响。方法:体外培养3组人群[ACS组(15例)、稳定型心绞痛组(SAP组,13例)与对照组(15例)]的PBMC,CRP(20μg/ml)刺激24h。普伐他汀以不同浓度(0.1×10-6,1×10-6,5×10-6,10×10-6mol/L)预先孵育ACS组PBMC2h后继以CRP刺激24h。酶联免疫吸附试验(ELISA)分析培养液上清中的IL-6水平,RTPCR分析细胞IL6mRNA表达水平。结果:20μg/mlCRP刺激状态下3组的IL-6分泌均较其基础状态显著增加(P<0.05),CRP明显增加PBMCIL-6的分泌;ACS组PBMC受CRP刺激后IL-6表达水平为(3129.5±333.4)ng/L,较对照组(987.3±102.3)ng/L和SA组(990.9±134.8)ng/L明显增高(P<0.05)。普伐他汀以剂量依赖方式下调ACS组PBMCIL6mRNA表达和IL-6分泌。结论:CRP明显增强ACS组PBMCIL6mRNA表达和IL-6分泌。一定浓度的CRP能诱导血单核细胞IL-6表达增加,在ACS患者中更为明显,普伐他汀有效降低CRP对ACS患者单核细胞的致炎症效应。更多还原

【Abstract】 Objective:The accumulating evidence suggests that C-reactive protein (CRP) may have direct inflammatory effects on the vascular wall and that statin therapy may have important non-lipid anti-inflammatory effects confirmed by decreasing serum inflammatory markers, such as CRP. However, the effect of pravastatin on interleukin-6 (IL-6) gene expression and release in cultured human monocytes from patients with acute coronary syndrome(ACS) was not investigated. Method: A prospective, human monocyte culture, statins intervention study. Monocytes were isolated from blood of patients with ACS and healthy volunteers by the Ficoll density gradient and stimulated by CRP (20 μg/ml)for 24 h. Also 0.1×10 -6, 1×10 -6,5×10 -6, 1×10 -5 mol/L pravastatin coincubated with cells in the presence of CRP. Measurements of supernatants of culture medium IL-6 were performed in duplicate using a commercial assay kit. The expression of IL-6mRNA was determined by RT-PCR method. Result: CRP induced the release of IL-6, with significantly elevated levels in cultured supernatants in ACS group, SA group and healthy group compared with their control respectively. A greater increase of IL-6 induced by CRP was detected in ACS group than in the other groups. CRP induces IL-6mRNA expression in monocytes from patients with ACS. Pravastatin significantly inhibited the expression and production of IL-6 in monocytes stimulated by CRP in a dose-dependent manner. Conclusion:CRP could induce more IL-6 release in human monocyte from patients with ACS than from healthy volunteer and stable angina patients,which may contribute to the mechanism of coronary artery disease in addition to being an incidental product of various types of systemic inflammation. Pravastatin could inhibit this response in a dose-dependent manner in ACS group, which may provide a new insight into the mechanisms of anti-inflammatory or anti-atherosclerotic actions of pravastatin.更多还原