香术防感方吸嗅与滴鼻给药方式预防甲型流感H1N1模型小鼠的药效学比较研究  

Comparative Study on the Pharmacodynamics of Xiangzhu Fanggan Formula(香术防感方)by Sniffing and Nasal Drops for Prevention of Influenza A H1N1 Virus Infection in Mice

作　　者：张悦 董毅智 李皓月 吴新新 黎晓蕾 赵静[1] ZHANG Yue;DONG Yizhi;LI Haoyue;WU Xinxin;LI Xiaolei;ZHAO Jing(Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing,100700;International Cooperation Department,China Academy of Chinese Medical Sciences)

机构地区：[1]中国中医科学院中医临床基础医学研究所,北京市东城区100700 [2]中国中医科学院国际合作处

出　　处：《中医杂志》2024年第12期1279-1286,共8页Journal of Traditional Chinese Medicine

基　　金：中国中医科学院科技创新工程中医临床基础学科创新团队项目(CI2021B003);中国中医科学院科技创新工程项目(CI2021A00704-4)。

摘　　要：目的比较香术防感方吸嗅和滴鼻两种经鼻给药方式预防甲型流感H1N1的有效性及可能作用机制。方法将56只BALB/c小鼠随机分为正常组、模型组、扎那米韦组、香囊高浓度组、香囊低浓度组、滴鼻高浓度组、滴鼻低浓度组,每组8只。香囊低、高浓度组分别给予15、30 g香术防感方香囊吸嗅,每天持续24 h;滴鼻低、高浓度组分别给予浓度为0.11、0.22 g/ml香术防感方滴鼻液滴鼻,每次20μl,每日2次;扎那米韦组给予浓度为1.025 mg/ml扎那米韦溶液滴鼻,每次20μl,每日2次;正常组、模型组滴鼻20μl生理盐水,每日2次。各组预防性干预5天。第5天给药1 h后,除正常组外,其余各组小鼠每只滴鼻35μl、50 LD50 A/PR/8/34/H1N1病毒液滴鼻,以制备甲型流感H1N1模型小鼠。于实验第5天至9天每日记录小鼠体质量及计算体质量变化率,并观察一般状态。于第9天取材,计算小鼠肺指数及肺指数抑制率;HE染色法检测肺组织病理变化,并进行肺组织病变评分;RT-qPCR法检测肺组织病毒载量;ELISA法检测上呼吸道灌洗液中分泌型免疫球蛋白A(sIgA)及血清肿瘤坏死因子α(TNF-α)、白细胞介素2(IL-2)、白细胞介素6(IL-6)、干扰素γ(IFN-γ)含量。结果实验第7、8、9天,模型组小鼠体质量变化率较同时间点正常组显著降低(P<0.05或P<0.01);实验第8、9天与模型组比较,扎那米韦组和滴鼻高浓度组小鼠体质量变化率增加(P<0.05或P<0.01)。与正常组比较,模型组小鼠肺指数、肺组织病变评分、肺组织病毒载量明显升高,血清TNF-α、IL-6、IL-2、IFN-γ含量明显升高,上呼吸道灌洗液sIgA水平明显降低(P<0.01)。与模型组比较,扎那米韦组和滴鼻高浓度组肺指数、肺组织病毒载量降低,血清IFN-γ、TNF-α、IL-2、IL-6含量降低,sIgA水平升高(P<0.05或P<0.01);除香囊低浓度组外,其余各药物干预组肺组织病变评分较模型组降低(P<0.01)。与扎那米韦组比较,香囊低�Objective To compare the effectiveness and mechanism of Xiangzhu Fanggan Formula(香术防感方)by sniffing and nasal drops for preventing influenza A H1N1flu.Methods Fifty-six BALB/c mice were randomly divided into normal group,model group,zanamivir group,high-concentration sachet group,low-concentration sachet group,high-concentration nasal drops group,and low-concentration nasal drops group,with 8 mice in each group.In the low-and high-concentration sachet groups,15 g and 30 g of Xiangzhu Fanggan Formula sachet were used for sniffing for 24 h per day;while in the low-and high-concentration nasal drops groups,nasal drops of Xiangzhu Fanggan Formula were given at a concentration of 0.11 and 0.22 g/ml,20μl each time,twice a day;in the zanamivir group,zanamivir was given at a concentration of 1.025 mg/ml of 20μl each time,twice a day;in the normal group and the model group,nasal drops of normal saline were given at 20μl each time,twice a day.Each group was given prophylactic intervention for 5 days.On day 5,1 h after the administration of the drug,the mice in all groups except the normal group received 35μl of 50 LD50 A/PR/8/34/H1N1 viral solution as nasal drops to prepare influenza A H1N1 model mice.The body mass of the mice was recorded and the rate of change of body mass was calculated daily from day 5 to day 9 of the experiment,and the general status was observed.The mice were sampled on day 9,and the lung index and the inhibition rate of lung index were calculated;HE staining was used to detect pathological changes in lung tissues and to score lung tissue lesions;RT-qPCR was used to detect viral load in lung tissues;and ELISA was used to detect secretory immunoglobulin A(sIgA)and serum tumour necrosis factorα(TNF-α)and interleukin 2(IL-2),interleukin 6(IL-6),and interferonγ(IFN-γ)in the lavage fluid of the upper respiratory tract.Results On days 7,8 and 9 of the experiment,the rate of change in body mass of mice in the model group significantly lower than that in the normal group at the same time poi

关 键 词：甲型流感 H1N1病毒 香术防感方 吸嗅 滴鼻 抗病毒 炎症因子 

分 类 号：R285.5[医药卫生—中药学]