阿司匹林对川崎病小鼠的治疗作用及其机制研究  

Study on the treatment of aspirin for Kawasaki disease in mice and its possible mechanism

作　　者：朱增燕[1] 黄艳[1] 施丹枫 薛洁[2] 

机构地区：[1]苏州大学附属儿童医院药剂科,江苏苏州215003 [2]苏州大学医学部药学院药理学系

出　　处：《临床心血管病杂志》2016年第1期59-62,共4页Journal of Clinical Cardiology

基　　金：苏州药学会-常州四药临床药学科研基金(No:SYSD2013146);苏州市2012年度科技发展计划(No:SYS201249)

摘　　要：目的：采用干酪乳杆菌细胞壁提取物（LCWE）诱导川崎病（KD）小鼠模型,探讨阿司匹林对KD小鼠的治疗作用及其可能的新的作用机制。方法：采用LCWE诱导KD小鼠模型,给予6.25~25.00mg/ml阿司匹林治疗10d,观察小鼠实验期间的一般情况和冠状动脉（冠脉）病变情况,以及测定小鼠血清中肿瘤坏死因子α（TNF-α）、前列腺素E2（PGE2）、基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶组织抑制因子-1（TIMP-1）含量,并计算MMP-9/TIMP-1比值。结果：小鼠单次腹腔注射LCWE后,在前3d内,KD小鼠进食、饮水、活动量明显减少;给阿司匹林治疗10d后,与正常对照组比较,KD小鼠冠脉周围有大量炎细胞浸润,血清中TNF-α和PGE2含量显著升高（P〈0.01）,同时伴有MMP-9、TIMP-1以及MMP-9/TIMP-1比值的明显升高（P〈0.05）,而阿司匹林组小鼠则冠脉周围炎性细胞明显减少,还能不同程度降低血清中TNF-α、PGE2、MMP-9的含量,以及降低MMP-9/TIMP-1比值（P〈0.05或P〈0.01）。结论：阿司匹林对KD引起的冠脉损伤有一定的疗效,可能与降低KD小鼠血清中的炎性因子TNF-α和PGE2的含量,以及降低与细胞外基质降解密切相关的MMP-9含量和MMP-9/TIMP-1比值有关。Objective：In this study,Lactobacillus casei cell wall extract（LCWE）was used to induce murine model of Kawasaki disease（KD）.Then we try to explore aspirin＇s treatment on KD mice and the possible new mechanism.Method：Using LCWE to induce KD murine model,then the mice were treated with aspirin 6.25-25mg/ml for 10 days.The general conditions were observed during the experiment,the coronary artery lesion was evaluated,and the level of serum tumor necrosis factor-α（TNF-α）,prostaglandin E2（PGE2）,matrix metalloproteinase-9（MMP-9）and tissue inhibitor of metalloproteinase-1（TIMP-1）were determined respectively.The ratio of MMP-9/TIMP-1was calculated.Result：After the mice were intraperitoneal injected of LCWE alone,the food intake,water intake,and the activity of KD mice were all obviously reduced during the first three days.After aspirin＇s treatment for 10 days,the inflammatory infiltration was found around coronary artery,and the serum levels of TNF-αand PGE2 were significantly increased in KD mice（P〈0.01）,and the levels of MMP-9,TIMP-1and the ratio of MMP-9/TIMP-1were also obviously increased simultaneously（P〈0.05）,while the inflammatory infiltration was reduced,and the level of TNF-α,PGE2,MMP-9and the MMP-9/TIMP-1ratio was decreased respectively after treated with aspirin（P〈0.05 or P〈0.01）.Conclusion：These results indicated that aspirin might have a certain treatment effect on coronary artery damage caused by KD,which maybe related to the simultaneously reduced TNF-α,PGE2,MMP-9and MMP-9/TIMP-1ratio.

关 键 词：川崎病 阿司匹林 炎性因子 基质金属蛋白酶-9 基质金属蛋白酶组织抑制因子-1 

分 类 号：R542.2[医药卫生—心血管疾病]