查尔酮类化合物L2H17对甲型流感病毒FM1株感染小鼠的保护作用  

Protective effect of chalcone ketones compound L2H17 on mice infected with influenza virus

作　　者：史鹏辉[1,2] 李剑波[2] 梁广[3] 张亚利[3] 王晓龙[1,2] 杨静[2,4] 王升启[2,4] 

机构地区：[1]山东中医药大学药学院,济南250355 [2]军事医学科学院放射与辐射医学研究所,北京100850 [3]温州医科大学药学院化学生物学研究中心,浙江温州325035 [4]河南中医药大学,郑州450046

出　　处：《军事医学》2017年第4期260-264,286,共6页Military Medical Sciences

基　　金：国家自然科学基金重点资助项目(81230089);国家自然科学基金面上项目(81473184;31270197)

摘　　要：目的研究查尔酮类化合物(代号:L2H17,简称L2)对流感病毒感染小鼠的保护作用及引起的病毒性肺炎的治疗作用。方法将小鼠随机分为6组:正常组、模型组、阳性药奥司他韦(达菲)组(20 mg/kg)、L2 20、40、80mg/kg剂量组,适应性喂养72 h,滴鼻(IN)造模,于造模前24 h给药,连续给药6 d观察至14 d,统计各组小鼠的中位生存时间、死亡保护率和生命延长率,观察L2对流感病毒感染小鼠的保护作用;按上法于造模后第3、5天无菌条件取小鼠全肺,计算肺指数及肺指数抑制率,左肺用4%甲醛固定,用于病理组织切片;右肺浸泡于RNAstore,检测肺组织病毒载量;小鼠摘眼球取血,采用双抗体夹心ELISA法检测小鼠血清中炎症细胞因子IL-6、TNF-α含量,观察L2对流感病毒感染引起的病毒性肺炎的治疗作用。结果与模型组相比,L2 80 mg/kg剂量组死亡率下降50%,中位生存时间、死亡保护率、生命延长率均有所提高;造模后第3、5天,L2 80 mg/kg剂量组肺指数降低,病理形态也有所改善;小鼠肺组织病毒载量降低(P<0.05);炎症因子IL-6含量较模型组有不同程度的降低。结论L2对流感病毒感染小鼠具有一定的保护作用,能减轻流感病毒所致肺炎的病变程度。Objective To investigate the protective and therapeutic effect of chalcone ketones compound（code：L2H17,hereinafter referred to as L2） on mice infected with influenza A virus.Methods BALB/c mice were randomly divided into six groups：normal group,model group,positive drug-treated group,L2 treated groups（3 different concentrations）.The mice were adapted for 72 hours,before a model was established by intranasal infection.Mice in each group were given medicine by i.g once daily for 6 days starting 24 h before virus challenge.Survival was observed daily for 14 days.The mortality,median survival time,rate of death protection and rate of prolonging life were determined to observe the therapeutic effect of chalcone（L2） against influenza virus infection.The whole lungs were taken under aseptic conditions on days 3 and 5 postinfection to calculat lung indexes and lung index inhibition.The left lung was fixed with 4% formaldehyde for pathological biopsy,the right lung was soaked in RNAstore to detect lung tissue viral load,and the double antibody sandwich ELISA method was used to detect the expression of inflammatory cytokines IL-6 and TNF-α in order to observe the therapeutic effect of L2 on viral pneumonia caused by influenza virus infection.Results Compared with the model group,the L2 80mg/kg treatment group exhibited significant increases in median survival time（11 d）,the rate of death protection（50%）,and the rate of prolonging life（24.1%） but a moderate 50% decrease in mortality.In addition,the lung index decreased significantly both on d 3 and 5 after virus infection（P〈0.05）.The pathological results also improved significantly.The L280 mg/kg dose group had a significantly lower viral load of lung tissue on d 3 and 5 post-infection（P〈0.05）.Compared with model group,the expression of inflammatory factor IL-6 became lower to different degrees.Conclusion L2 has a protective effect on mice infected with influenza virus by reducing the degree of pathological changes of pneumonia cause

关 键 词：流感病毒A型 病毒性肺炎 查尔酮类化合物 肿瘤坏死因子Α 白细胞介素6 

分 类 号：R511.7[医药卫生—内科学]