溶酶体酶B抑制剂CA-074Me对病毒性心肌炎小鼠心肌保护作用的研究  

Effect of Cathepsin B Inhibitor CA-074Me on the Model of Mice Viral Myocarditis

作　　者：张新刚[1] 赵刚[1] 李双杰[2] 李高平[1] 陈瑞珍[1] 杨英珍[1] 

机构地区：[1]复旦大学附属中山医院心内科,上海200032 [2]湖南省南华大学附属第一医院,湖南衡阳421001

出　　处：《中国临床医学》2008年第6期741-743,共3页Chinese Journal of Clinical Medicine

基　　金：国家自然科学基金资助项目(NO:30271665)

摘　　要：目的：观察溶酶体酶B（Cathepsin B）抑制剂CA-074Me对病毒性心肌炎小鼠的干预作用，并探讨其对心肌保护的作用机制。方法：55只4周龄雄性BALB／c小鼠随机分为正常对照组（N组，n=10）、病毒模型组（V组，n=15）、低剂量干预组（L组，n=15）及高剂量干预组（H组，n=15）。后3组经腹腔接种柯萨奇病毒B3（CVB3）成功诱发急性病毒性心肌炎，L组和H组于病毒接种后第2天分别腹腔注射CA074Me0．4mg·kg^-1和4mg·kg^-1，均连续用7d（第2～8天），第15天处死全部存活小鼠，并采血检测血清cTnI以及收集小鼠心脏标本作组织学检测。结果：小鼠感染CVB后，其心肌组织中Cathepsin B蛋白表达水平及血清cTnI明显增加；经CA-074Me干预后，Cathepsin B表达以及cTnI降低，心肌损害减轻，小鼠生存率升高，尤其以H组最明显。结论：CA-074Me通过抑制Cathepsin B的表达，减轻心肌损害、提高感染小鼠的存活率，起到保护性的作用，并且对心肌细胞的保护存在明显的量效关系，可为今后临床治疗病毒性心肌炎的研究提供参考。Objective：To observe the intervention effect of CA-074Me on the model of mouse viral myocarditis, and to explore the possible mechanism of its protection on myocardium. Methods： A total of 55 male 4-week-old BABL/c mice were randomly divided into 4 groups： normal control group （group N, n = 10）, viral myocarditis group （group V, n = 15）, CVB3 infected and low dose CA-074Me treated group （group L, n = 15） and CVB3 infected and high dose CA074Me treated group （group H, n = 15）. Every mouse in the experimental group was given 0.1 ml coxsackie B3 virus intraperitonealiy , At the same time, 0.1 ml of normal saline was treated in group N. From day 2 to day 8, 0.4mg/kg and 4mg/kg Ca-074Me were given intraperitoneally per day in group L and H mice respectively. On day 15 the serum was collected to detect cardiac troponin I （cTnI）, then all of mice were sacrificed and hearts were removed for histologic study on day 15. Results： The cathepsin B expressional levels and serum cTnI levels were increased remarkably after CVB3 inoculation. In each of CA-074Me treatment groups, cTnI levels were markedly decreased, meanwhile, the myocardial damage was attenuated and mice survival rate was elevated compared with viral myocarditis group, especially high close CA074Me group. Conclusion： CA074Me can attenuate the myocardium injury, and re duce the mortality of mouse with CVB3 myocarditis by inhibition of cathepsin B expression. And the relation between dose and effect is obvious in protecting the myocardium. The study may be a new method for treating viral myocarditis in the future.

关 键 词：CATHEPSIN B CA-074Me 病毒性心肌炎 心肌肌钙蛋白-I 

分 类 号：R542.21[医药卫生—心血管疾病]