反义硫代寡核苷酸对小鼠柯萨奇病毒B_3性心肌炎影响的研究

Study on effect of antisense phosphorothioate oligodeoxynucleotide on CVB_3-myocarditis in mice

目的 :观察AODN对小鼠病毒性心肌炎的影响。方法 :选取4～6周龄雄性Balb/C鼠(体重18～20g)48只,随机分为6组,8只/组,其中正常对照和病毒对照各1组,4个实验组。正常对照组小鼠腹腔内注射0.1mlRPMI1640,其它5组小鼠腹腔内接种0.1mlCVB3(200TCID50),半小时后4个实验组小鼠腹腔内注射0.2ml不同剂量的AODN ,正常对照组和病毒对照组分别注射0.2mlAODN媒体溶液。7天后测定血清LDH活性 ,并且进行心肌组织病理学检查。结果 :随注射AODN剂量增加,血清LDH活性逐渐降低 ;心肌细胞变性、坏死及间质炎性细胞浸润程度逐渐减轻 ;心肌炎发病率也逐渐降低。结论:AODN可保护小鼠心肌组织抵抗CVB3

Objective:To investigate the effect of antisense oligodeoxynucleotide (AODN) on CVB3- myocarditis in Balb/C mice.Methods:Forty-eight male Balb/C mice (4～6 weeks old) were divided randomly into 6 groups, 8 mice per group. 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(i.p.) with 100 μl of RPMI1640 medium containing 200 TCID 50 of CVB 3 and followed by 200 μl of different doses of liposomally endocapsulated antisense phosphorothioate oligodeoxynucleotide(AODN)in 4 experimental groups and by 200 μl of vehicle solution of AODN in viral control group 30 minutes later. Mice of normal control group were first inoculated i.p.100 μl of RPMI1640 medium and followed by 200 μl of vehicle solution of AODN 30 minutes later. At seventh day of postinfection all mice were killed and blood samples were collected for detecting serum LDH level. Hearts were removed aseptically for detecting cardiac histological lesions.Results: Serum LDH level of viral control group was significantly higher than that of normal control group, but LDH levels of 4 experimental groups were between that of viral control group and that of normal control group, and LDH levels decreased accompaning with AODN dose increasing. Lightened cardiac lesions and decreased morbidity of myocarditis in 4 experimental groups were found. And these effects were in dose dependent manner. Conclusion:AODN can protect myocardial tissue against CVB3 infection.