阿托伐他汀通过下调PAPP-A、MMP3 mRNA表达抑制rhCRP诱导的人动脉平滑肌细胞炎症反应  

Atrovastatin ameliorates rhCRP-induced human arterial smooth muscle cell inflammatory responses via down-regulation of PAPP-A and MMP-3 mRNA expression

作　　者：廖丽贞[1] 唐凯[2] 梅卫义[2] 陆立鹤[3] 

机构地区：[1]广东药学院健康学院,广东广州510310 [2]中山大学附属第一医院黄埔院区心内科,广东广州510370 [3]中山大学中山医学院病理生理学教研室,广东广州510080

出　　处：《广州医学院学报》2013年第6期10-14,共5页Academic Journal of Guangzhou Medical College

基　　金：广东省科技计划基金项目(2010B0316000068;2011B031800137);高校基本科研业务费"中山大学青年教师培育计划"(11ykpy8)

摘　　要：目的:探讨阿托伐他汀(ATO)对人重组C反应蛋白(rhCRP)诱导的人动脉平滑肌细胞炎症反应的影响及其机制是否与下调妊娠相关性血浆蛋白-A(PAPP-A)、基质金属蛋白酶3(MMP3)mRNA表达相关。方法:应用不同浓度rhCRP(1、5、10、20 mg/L)处理人动脉平滑肌细胞不同时间(3、6、12、24 h),采用ELISA法检测炎症因子IL-6、IL-8水平,以确定炎症模型建立条件。不同时相点加入10^(-7)mol/L ATO后,ELISA法再次检测IL-6、IL-8水平;RT-PCR法测定PAPP-A、MMP3 mRNA表达水平。结果:不同浓度rhCRP处理人动脉平滑肌细胞不同时间后,人动脉平滑肌细胞培养基中的IL-6、IL-8呈浓度依赖性和时间依赖性增加(P<0.05)。采用10 mg/L rhCRP处理12 h作为人动脉平滑肌细胞炎症模型建立的条件。ATO 10-7 mol/L预处理、共处理均能有效抑制rhCRP所致的IL-6、IL-8升高(P<0.05),同时也能抑制rhCRP所致的PAPP-A、MMP3 mR NA表达升高(P<0.05);而ATO后处理组IL-6、IL-8水平及PAPP-A、MMP3 mRNA表达水平与rhCRP模型组比较,差异无统计学意义(P>0.05)。结论:AT0具有抑制出CRP诱导的人动脉平滑肌细胞炎症反应的作用,此作用可能与其下调PAPP-A、MMP3 mRNA表达有关。Objective：To investigate the effects of atrovastatin （ATO） on human recombinant C-reactive protein （rhCRP）-induced human arterial smooth muscle cell inflammatory response, and to determine whether these effects are associated with the down-regulation of pregnancy-associated plasma protein-A （PAPP-A） and matrix metalloproteinase-3 （ MMP-3 ） mRNA expression. Methods ： The human arterial smooth muscle cells were incubated with different concentrations of rhCRP （ 1,5, 10 and 20mag/L） for various periods （3, 6, 12 and 24 hours） , which was followed by the measurement of IL-6 and IL-8 by using enzyme-linked immunosorbent assay （ELISA） to determine the optimal conditions for constructing the inflammatory model. Followng the addition of 10-7mol/L ATO, the levels of IL-6 and IL-8 were reassessed by ELISA. In addition, reverse transcriptase polymerase chain reaction was employed to determine the levels of PAPP-A and MMP3 mRNA. Results：Following incubation with different concentrations of rhCRP, the levels of IL-6 and IL-8 increased in a time- and concentration-dependent fashion （ both P 〈 0.05）. It was found that a 12-hour administration of 10 mg/L rhCRP was the optimal condition for constructing the human arterial smooth muscle cell inflammatory model. Preconditioning or co-incubation with 10-7 mol/L ATO both effectively attenuated the rhCRP-induced increase in IL-6 and IL-8 （ both P 〈 0.05 ） and suppressed the augmentation of PAPP-A and MMP-3 mRNA expression （both P 〈 0.05）. However, there was no marked difference in the levels of IL-6, IL-8, PAPP-A and MMP-3 mRNA betweenATO treatment group and rhCRP model group（P 〉0.05）. Conclusion： ATO attenuates rhCRP- induced human arterial smooth muscle cell inflammatory responses possibly via the down-regulation of PAPP-A and MMP-3 mRNA expression.

关 键 词：阿托伐他汀 炎症因子 妊娠相关性血浆蛋白-A 基质金属蛋白酶3 

分 类 号：R363[医药卫生—病理学]