摘要
目的:观察C-反应蛋白(CRP)刺激对人脐静脉血管内皮细胞(HUVECs)分泌功能的影响。方法:体外培养HUVECs,检测细胞对CRP诱导的反应以及普伐他汀干预效应。酶联免疫吸附试验检测培养液上清中肿瘤坏死因子α(TNF-α)和白介素-6(IL-6)的水平。电泳漂流技术(EMSA)检测细胞核提取物中NF-κB与DNA的结合活性。结果:TNF-α和IL-6的水平随CRP刺激浓度的升高而增加,呈剂量依赖性(0-100 mg/L),在5 mg/L CRP时即可检测到TNF-α和IL-6表达,100 mg/L CRP时可见最大效应。50 mg/L CRP呈时间依赖性增加TNF-α和IL-6的表达(0-48 h),24 h达高峰。普伐他汀有效抑制CRP诱导的NF-κB激活和炎症因子表达。结论:CRP剂量依赖性激活血管内皮细胞的炎症因子表达,其中NF-κB途径被激活,参与致动脉粥样硬化作用;他汀类药物能有效抑制该途径,发挥抗炎及抗动脉粥样硬化作用。
Objective： To investigate the mechanism underlying the role of C-reactive protein （CRP） in endothelial cells and the effect of statin on inflammatory factors such as tumor necrosis factora （TNF-α） and interleukin-6 （IL-6） stimulated by CRP. Methods： The response of vascular endothelial cells （HUVECs） to CRP was investigated and compared with the response to lipopolysaccharide （LPS）. Further we observed whether the redox-responsive transcription factor NF-kappaB（NF-κB） involved in this response of HUVECs by CRP. At last the effects of pravastatin were observed. Results： The present study showed that CRP increased the release of TNF-α and IL-6 as well as LPS did in HUVECs. In HUVECs induction of TNF-α and IL-6 was already presented at 5 mg/L and reached a maximum at 100 mg/L of CRP, at which point a substantial increase in expression of TNF-α and IL-6 were evident. The CRP effect was time-dependent （0-48 h） and dose-dependent （0-100 mg/L）. tivation were inhibited by pravastatin. CRP induced activation of NF-κB in HUVECs and the activation were inhibited by pravastatin. Conclusion： CRP causes NF-κB activation of HUVECs which could lead to the induction of TNF-α and IL-6 as well as LPS does. This effect can be inhibited by pravastatin. CRP may play a role in atherogenesis by activating endothelial cells at least in part through NF-κB and statins inhibit this response, which may provide an insight into the mechanisms of anti-inflammatory or anti-atherosclerotic actions of statins.
出处
《武汉大学学报（医学版）》
CAS
2008年第2期198-201,共4页
Medical Journal of Wuhan University
