摘要
目的:观察针对小鼠巨细胞病毒(MCMV)即刻早期基因1(IE-1)的小分子干扰RNA片段(siRNAs)对小鼠巨细胞病毒性心肌炎的治疗作用。方法:无病原体的BALB/c小鼠120只,4周龄,雄性,重10-12g,随机分为6组,20只/组,其中对照和MCMV病毒感染组各1组及4个MCMV IE-1 siRNA治疗组。对照组小鼠腹腔内注射0.1mL DMEM液,其它5组小鼠腹腔内接种0.1mL含TCID5010-4 MCMV的DMEM液,30min后4个MCMV IE-1 siRNA治疗组小鼠腹腔内注射0.2mL不同剂量的MCMV IE-1 siRNA,对照和MCMV病毒感染组分别注射0.2mL siRNA媒体溶液。实验第7、14、21、28、35、42、49、56、63和70d测定心肌酶谱肌酸激酶(CK)、肌酸激酶同功酶(CK-MB)、谷草转氨酶(GOT)、乳酸脱氢酶(LDH)和LDH1/LDH2活性,并且进行了心肌组织病理学、超微病理学和髓过氧化物酶(MPO)和MCMV IE-1的检查。结果:随注射siRNA剂量增加,心肌炎发病率也逐渐降低;心肌细胞变性、坏死及间质炎性细胞浸润程度和超微病理变化逐渐减轻;血清心肌酶谱(CK、CK-MB、GOT、LDH和LDH1/LDH2)活性逐渐降低;心肌组织MPO下降;心肌细胞中MCMV IE-1表达减弱。siRNA对病毒性心肌炎疗效的影响是剂量依赖性的。结论:针对MCMV IE-1 siRNA可抗MCMV病毒感染,保护小鼠心肌组织。
AIM： To investigate the effect of siRNA on myocarditis induced by MCMV in BALB/c mice. METHODS： One handred and twenty male BALB/c mice （4 weeks old） were divided randomly into 6 groups with 20 mice each. Among these groups, one normal control group, one viral control group and 4 experimental groups were assigned. Mice in viral control and 4 experimental groups were inoculated intraperitoneally injection （ip） with 100 μL of DMEM medium containing TCID50 10^-4 MCMV, and followed by 200 μL of different doses of liposomally endocapsulated siRNA in 4 experimental groups and by 200 μL of vehicle solution of siRNA in viral control group 30 min later. Mice in normal control group were first inoculated ip 100 μL of DMEM medium and followed by 200 μL of vehicle solution of siRNA 30 min later. At day 7, 14, 21,28, 35, 42, 49, 56, 63 and 70 of postinfection, all mice were killed and blood samples were collected for detecting serum zymogram （CK, CK- MB, GOT, LDH and LDH1/LDH2 ） and the anti -cardiac β1 receptor autoantibody titer level. Hearts were removed aseptically for detecting cardiac histological lesions and uhrastructure changes. RESULTS： Decreased morbidity of myocarditis, lightened cardiac pathologic lesions and uhrastructural changes in 4 experimental groups were observed. Serum zymogram （ CK, CK - MB, GOT, LDH and LDH1/LDH2 ） and β1 antoantibody titer level in viral control group were significantly higher than those in normal control group, but zymogram and β1 autoantibody titer levels in 4 experimental groups were between those in viral control group and normal control group. The activities of CK, CK - MB, GOT, LDH and LDH1/LDH2 and β1 autoantibody titer level decreased accompanied with siRNA dose increasing. These effects were in a dose dependent manner. CONCLUSION： siRNA protects myocardial tissue against MCMV infection.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2008年第11期2132-2137,共6页
Chinese Journal of Pathophysiology
基金
湖北省教育厅基金资助项目(No.D200526003)
广东食品药品职业学院立项课题
