摘要
目的观察组织蛋白酶B(cathepsinB)抑制剂CA-074Me对病毒性心肌炎小鼠的干预作用。方法55只雄性BALB/c小鼠随机分为正常对照组(N组,n=10)、心肌炎对照组(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)。后三组经腹腔接种柯萨奇病毒(CVB3m)诱发急性心肌炎,L组和H组于病毒接种后第2d分别腹腔注射CA-074Me0.4mg/kg和4mg/kg,均连续使用7d(2～8d),第15d处死全部存活小鼠并取其心脏,采用RT-PCR和免疫组化等方法半定量分析各组小鼠心肌组织中cathepsinB基因转录及蛋白表达水平。结果V组与N组比较,心肌中cathepsinBmRNA及蛋白表达水均明显增加(P<0.05);L组与V组比较,心肌中cathepsinBmRNA和蛋白表达量降低(P<0.05),小鼠生存率虽然有所升高,但差异无显著性(P>0.05);H组与V组相比,心肌组织中cathepsinBmRNA和蛋白表达量显著降低(P<0.01),心肌损害减轻,小鼠生存率明显升高,差异有高度统计学意义(P<0.05)。结论CA-074Me通过抑制cathepsinB的表达,减轻心肌损害,提高感染小鼠的存活率,对Balb/c小鼠CVB3心肌炎具有良好的治疗作用。
Objective To investigate the effects of CA-074Me on viral myocarditis in mice.Methods Fifty-five male Balb/c aged at4weeks were randomly divided into4groups:normal control group(group N,n=10),viral myocarditis control group(group V,n=15),low dose CA-074Me treatment group(group L,n=15)and high dose CA-074Me treatment group(group H,n=15).Acute myocarditis was induced with intraperitoneal injection of0.1ml Coxsackie B 3 virus to each mouse in the later three groups.At the same time,each mouse in normal control group received intraperitoneal injection of0.1ml normal saline.From day2to day8,mice in group L or group H received consecutive intraperitoneal injection of CA-074Me0.4mg/(kg·d)or4mg/(kg·d)and mice in group N and group V0.1ml DMSO.On day14,all mice were killed.Expression levels of myocardial cathepsin B mRNA and protein were determined with RT-PCR and immunohistochemistry respectively.Results Expression levels of cathepsin B mRNA and protein in group V were higher than those in group N(P<0.05),whereas expression levels in group L were lower than those in group V(P<0.05).The survival rate in group L was higher than that in group V but without statistical significance(P>0.05).Expression levels in group H were much lower than those in group V(P<0.01).The survival rate in group H was higher than that in group V with statistical significance(P<0.05).Con-clusions CA-074Me is an effective agent for anti-CVB3infection,suppressing excessive expression of cathepsin B may play an important role to protect the heart injure in Balb/c mice with CVB 3 viral myocarditis.
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2005年第1期52-54,59,共4页
Journal of Clinical Pediatrics
基金
国家自然科学基金资助(项目编号:30271665)
