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为了在动物整体水平评价流感泰得 (flutide ,FT)抗流感病毒活性 ,建立了流感病毒感染小鼠实验模型 ,并测定了FT在小鼠模型中的抗病毒活性和对小鼠的急性毒性作用。结果表明 ,流感病毒A 京防 86 1(H1N1)和A 沪防 93 9(H3N2 )在小鼠体内连续传代 6次时即对小鼠具有感染性 ,表现为小鼠体重下降 ,小鼠肺脏湿重增加并能检测到很高的病毒滴度。在小鼠模型中FT具有较高的抗病毒活性 ,表现在FT能明显提高病毒感染小鼠的存活率 ,抑制病毒感染引起的小鼠体重下降和肺湿重增加。当FT剂量为 6.5× 10 -4μmol g和 32 .5× 10 -4μmol g滴鼻给药时 ,小鼠存活率分别提高30 %和 5 0 % (P <0 .0 5 ) ;给药途径对FT抗病毒作用有一定影响 ,静脉注射高于腹腔注射和滴鼻给药 ;当接种剂量为 5 2× 10 -4μmol g时 ,FT对小鼠的生长状态、体重和肺脏湿重等均无影响。以上结果为抗流感病毒反义寡核苷酸药物研究向临床前试验过渡提供了试验依据。
In order to evaluate the flu-resistant (FT) anti-influenza virus activity at the animal level, an experimental model of influenza virus infection in mice was established and the antiviral activity of FT in mice and the acute toxicity to mice . The results showed that the influenza A virus 861 (H1N1) and A Shanghai anti-93 9 (H3N2) mice in vivo continuous passage 6 times that the mice were infectious, the performance of the mouse weight loss, mouse lung wet Heavy up and can detect high viral titers. FT has a high antiviral activity in a mouse model, which shows that FT can significantly improve the survival rate of virus-infected mice and inhibit the weight loss and lung wet weight of mice caused by virus infection. When the FT dose was 6.5 × 10 -4 μmol g and 32.5 × 10 -4 μmol g intranasally, the survival rate of mice increased by 30% and 50% (P <0.05), respectively. FT had an effect on the antiviral effect. Intravenous injection was higher than intraperitoneal injection and intranasal administration. FT did not affect the growth status, body weight and lung wet weight of mice when inoculated with a dose of 5 2 × 10 -4 μmol g . The above results provide the experimental basis for the study of anti-influenza virus antisense oligonucleotide drug to the preclinical test.