白细胞介素6对人冠状动脉平滑肌细胞基质金属蛋白酶系统分泌平衡的影响  

Influence of interleukin-6 on the secretion balance of matrix metalloproteinase system in human coronary arterial smooth muscle cells

作　　者：李丽[1] 张清华[2] 蒋知新[3] 高德禄[4] 谢声扬 李安全[4] 

机构地区：[1]南方医科大学,广东省广州市510515 [2]解放军第三○五医院心血管内科,北京市100017 [3]解放军第三○五医院老年病中心实验室,北京市100017 [4]解放军第三○五医院检验科,北京市100017

出　　处：《中国组织工程研究与临床康复》2007年第41期8271-8275,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：全军医药卫生"十五"计划课题(04LX048);全军医药卫生"十一五"计划科技攻关课题(06G144)~~

摘　　要：目的:研究表明,白细胞介素6等多种炎症因子与急性冠状动脉综合征斑块的稳定性下降有着密切联系;金属蛋白酶组织抑制因子的分泌失衡,也可能是斑块稳定性的原因之一。实验拟证明白细胞介素6对人冠状动脉平滑肌细胞的基质金属蛋白酶3及金属蛋白酶组织抑制因子1分泌平衡的影响。方法:实验于2006-12/2007-04在解放军第三○五医院老年病中心实验室完成。①实验材料:人冠状动脉平滑肌细胞(Casecade公司);白细胞介素6(PeProtech公司)。②实验过程:培养人冠状动脉平滑肌细胞,传代至5～7代。一期:分别加入0和10μg/L白细胞介素6(0μg/L为对照组)刺激人冠状动脉平滑肌细胞,分别孵育2,4,8,24,36h,收集细胞培养液上清。二期:分别采用0,5,10,50μg/L白细胞介素6刺激人冠状动脉平滑肌细胞(0μg/L为对照组),6h后收集细胞培养液上清。③实验评估:应用酶联接免疫吸附剂测定方法检测细胞培养液上清内基质金属蛋白酶3、金属蛋白酶组织抑制因子1的表达量。结果:①加入白细胞介素6后,基质金属蛋白酶3、金属蛋白酶组织抑制因子1的表达量在2h时开始增加,并随时间的延长而不断增加;随着白细胞介素6剂量的增加,表达量均不断增加。②基质金属蛋白酶3/金属蛋白酶组织抑制因子1在2h开始升高,8h达到顶峰,而后缓慢下降,与对照组比较,P均<0.05;随着白细胞介素6剂量的增加,表达量均不断升高,10μg/L和50μg/L组与对照组比较,P<0.05。结论:白细胞介素6可使人冠状动脉平滑肌细胞分泌不稳定斑块标记物--基质金属蛋白酶3、金属蛋白酶组织抑制因子1及基质金属蛋白酶3/金属蛋白酶组织抑制因子1增加,且呈剂量和时间依赖效应,说明炎症可能是急性冠状动脉综合征发生发展的机制之一。AIM： The studies have showed that interleukin-6 （IL-6） and other inflammatory factors are closely related with the decrease of plague stability of acute coronary syndrome. Meanwhile, secretion unbalance of tissue inhibitor of metalloproteinase （TIMP） may be one of the reasons for the plague stability. In this study, the effect of IL-6 on secretion balance of matrix metalloproteinase-3 （MMP-3） and TIMP-1 in human coronary arterial smooth muscle cells （HCASMCs） was observed. METHODS： The experiment was performed in the Central Laboratory of Geriatric Center, the 305 Hospital of Chinese PLA from December 2006 to April 2007. （1）HCASMCs （Casecede） were cultured and passaged to the fifth to seventh generations. At the first stage, the cells were stimulated with 10 and 0 μg/L IL-6 （PeProtech, 0 μg/L as control group）, and the culture media was collected after 2, 4, 8, 24 and 36 hours. At the second stage, HCASMCs were incubated with 0, 5, 10, 50 μg/L IL-6, respectively （0 μg/L as control group）, and the culture media was collected after 6 hours. （2） Concentrations of MMP-3 and TIMP-1 in cultural fluid were measured by ELISA. RESULTS： （1）The concentrations of MMP-3 and TIMP-1 were elevated after cultured with IL-6 time-dose dependently. （2） MMP-3/TIMP-1 was up-regulation after 2 hours, reached the peak at 8 hours, then began to descent slowly compared with control group （P 〈 0.05）; with the dose increase of IL-6, the secretion of MMP-3 and TIMP-1 was increased, and there were differences between 10 and 50 μg/L group and control group （P 〈 0.05）. CONCLUSION： IL-6 can induce the production of MMP-3 and TIMP-1, and increase MMP-3/TIMP-1 of HCASMAC in a time and dose-dependent manner, indicating inflammation may play an important role in the development of acute coronary syndrome.

关 键 词：冠状动脉疾病 炎症 白细胞介素6 基质溶解素1 金属蛋白酶类组织抑制剂 组织构建 

分 类 号：R392[医药卫生—免疫学]