目的: 研究馥感啉口服液对呼吸道合胞病毒(respiratory syncytial virus, RSV)感染小鼠的治疗作用。方法: 将120只ICR小鼠随机分为对照组,模型组,利巴韦林组,馥感啉5、10和20 g/kg组。采用滴鼻感染法感染RSV后,根据实验分组分别进行灌胃给药治疗,对照组及模型组用等量的生理盐水进行治疗处理,每日2次,共6 d。通过HE染色分析馥感啉口服液对小鼠肺病变的治疗情况,分别采用ELISA和RTPCR方法检测小鼠肺泡灌洗液及肺组织中IFNβ、IL6的含量及mRNA表达水平。流式细胞术检测小鼠外周血CD3+CD4+,CD3+CD8+水平。结果: 成功建立RSV感染小鼠模型。HE病理结果显示不同治疗方法对肺组织病变均有不同情况改善,其中以馥感啉10 g/kg组和20 g/kg组对小鼠肺组织病变改善作用最为明显。馥感啉口服液各剂量组小鼠IFNβ和IL6含量及mRNA表达水平随用药时间延长而逐渐降低;与对照组相比,模型组、利巴韦林组及馥感啉5 g/kg组CD3+CD4+水平显著升高(P均<0.05),馥感啉10 g/kg组和20 g/kg组CD3+CD4+显著降低(P均<0.05);与对照组相比,模型组CD3+CD4+/CD3+CD8+水平显著升高(P<0.05),馥感啉20 g/kg组显著降低(P<0.05),利巴韦林组、馥感啉5 g/kg组及10 g/kg组CD3+CD4+/CD3+CD8+水平与对照组相比,差异均无统计学意义(P>0.05)。结论: 馥感啉口服液各剂量组对小鼠RSV感染有一定的治疗效果,并在一定范围内存在剂量效应关系,高剂量组治疗效果更加显著。
Abstract
Objective: To study the therapeutic effect of Fu-ganlin oral liquid on respiratory syncytial virus(RSV) infection in mice. Methods: The 120 ICR mice were randomly divided into 6 groups, which with regular control group, infection model group, Ribavirin group (150 mg/kg), Fu-ganlin oral liquid group 5g/kg, Fu-ganlin oral liquid 10 g/kg group and Fu-ganlin oral liquid 20 g/kg group. These ICR mice were infected by RSV with intranasal infection method to make effective animal models. Then according to the experimental grouping, the treatment of gavage was carried out respectively. And the control group and the infection model group were treated with the same amount of physiological saline, 2 times a day and a total of 6 days . At last, we used HE staining to observe pathological changes in mice by Fuganlin oral liquid treatment after 6 days. In addition, IFN-β, IL-6 content and gene expression level with infected mice in alveolar lavage fluid and lung tissue were analyzed by ELISA and real time fluorescence quantitative PCR methods during the treatment. The peripheral blood was sampled and detected CD3+CD4+ and CD3+CD8+ levels after heparinization with flow cytometer Results: The mouse model of RSV infection was successfully established. The pathological results of HE staining showed that the pathological changes of lung tissue in different treatment groups were improved, and the Fu-ganlin oral liquid 10 g/kg and 20 g/kg groups in the mice were most significantly improved in the lung tissue. The level of IFN-β, IL6 and gene expression of mice lung tissue decreased gradually, and the peripheral blood level of the above inflammation factors in each treatment group was compared with the control group. Among them, The level of CD3+CD4+ in the model group, Ribavirin group and the Fu-ganlin oral liquid 5 g/kg group increased significantly(P<0.05); the CD3+CD4+ of the Fu-ganlin oral liquid 10g/kg and the 20 g/kg group decreased significantly(P<0.05). And the levels of CD3+CD4+/CD3+CD8+ in the model group increased significantly(P<0.05),the Fu-ganlin oral liquid 20 g/kg group were significantly decreased(P<0.05),the levels of CD3+CD4+/CD3+CD8+ in the Ribavirin group, Fu-ganlin oral liquid 5 g/kg and 10 g/kg groups had no significant difference. Conclusion: The treatment group of "Fuganlin oral liquid " has a promising therapeutic effect on RSV infection in mice in a dose-dependent manner. The effect of high dose group is more significant.
关键词
呼吸道合胞病毒 /
馥感啉口服液 /
ICR小鼠
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参考文献
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脚注
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基金
上海市综合医院中西医结合专项(ZHYY-ZXYJHZX-2-08);上海儿童医学中心横向课题
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