银翘散对FM1诱导肺炎小鼠肺组织中JAK/STAT信号转导通路及NS1蛋白、MxA蛋白表达的影响  

Influence of Yinqiao San on JAK/STAT Signal Pathway and Protein Expressions of NS1 and MxA in the Lung Tissue of Pneumonia Mice Induced by FM1

作　　者：王思源[1] 王文丽[1] 南春红[1] 王雪峰[1] Wang Siyuan;Wang Wenli;Nan Chunhong;Wang Xuefeng(Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China)

机构地区：[1]辽宁中医药大学附属医院,沈阳110032

出　　处：《中国药师》2020年第2期213-217,共5页China Pharmacist

基　　金：国家自然科学基金项目(编号:30772880)。

摘　　要：目的:研究银翘散对甲型流感病毒FM1诱导肺炎小鼠肺组织中非结构蛋白1(NS1)、黏病毒抗性蛋白A(Mx A)蛋白表达的影响及Janus激酶/信号转导与转录激活因子(JAK/STAT)信号传导机制。方法:将72只昆明小鼠随机分为6组:正常组、模型组、利巴韦林组(100 g·kg^-1·d^-1)及银翘散提取物高、中、低剂量组(17,6.8,3.4 g·kg^-1·d^-1),每组12只。除正常组外,其余各组建立FM1滴鼻感染的小鼠流感病毒性肺炎模型。感染后24 h,正常组和模型组给予双蒸水灌胃,治疗组分别予各药物治疗,连续3 d。以苏木素-伊红(HE)染色观察病理;免疫组化法测定肺组织中NS1、Mx A蛋白含量;Westen blot检测肺组织NS1、STAT1蛋白水平。结果:与正常组相比,其余各组的NS1、STAT1、Mx A蛋白表达差异均有统计学意义(P<0.05);模型组小鼠肺组织病变严重,NS1、STAT1蛋白水平明显升高(P<0.05);与模型组比较,利巴韦林组和银翘散各剂量组小鼠肺组织病变明显改善;小鼠肺组织中NS1、高剂量组STAT1蛋白表达明显降低,Mx A蛋白表达明显升高(P<0.05)。银翘散治疗病毒性肺炎存在一定的量-效关系。结论:在小鼠甲型流感病毒肺炎发病过程中,JAK/STAT信号通路处于激活状态,STAT1蛋白表达增强,机体NS1表达增强;银翘散治疗FM1肺炎有显著疗效,其机制可能是抑制流感病毒NS1和JAK/STAT信号通路的活化,刺激Mx A蛋白表达,从而达到减少肺组织损伤的治疗目的。Objective:To investigate the influence of Yinqiao San on JAK/STAT signal pathway and protein expressions of NS1 and MxA in the lung tissue of pneumonia mice induced by FM1.Methods:Totally 72 Kunming mice were randomly divided into 6 groups:the normal group,the model group,ribavirin group(100 g·kg^-1·d^-1),Yinqiao San high,medium and low dose groups(17,6.8 and 3.4 g·kg^-1·d^-1)with 12 mice in each group.FM1 virus was intranasally inoculated to mice in the other groups except the normal group for 3 days to establish pneumonia infection model.After 24 h infection,the mice in the normal group and the model group were intragastrically given double steamed water,and the mice in the other groups were intragastrically given the low,middle and high dose of Yinqiao San and ribavirin for 3 days.Immunohistochemistry staining was used to detect the expressions of NS1 and STAT1 protein in lung tissue.Western blot was used to detect the protein expressions of NS1 and MxA in lung tissue.Results:The expressions of NS1,STAT1 and MxA in pneumonia group were markedly higher than those in the normal control group(P<0.05).The pathological changes of lung tissue in the model group were serious,and the protein levels of NS1 and STAT1 were significantly increased(P<0.05).Compared with those in the model group,the pathological changes in the lung tissue of mice in ribavirin group and Yinqiao San group were obviously improved,the protein expressions of NS1 and STAT1 of high dose group in the lung tissue of mice decreased significantly,while the protein expression of MxA increased significantly(P<0.05).There was a dose-dependent manner between Yinqiao San and viral pneumonia.Conclusion:During the pathogenesis ofⅣpneumonia in mice,JAK/STAT signaling pathway is activated,STAT1 protein expression is enhanced,and NS1 expression is also enhanced.Yinqiao San has a significant effect in treating FM1 pneumonia.Its mechanism may be to inhibit influenza virus NS1,thereby inhibiting the activation of JAK/STAT signaling pathway and stimulating th

关 键 词：银翘散 甲型流感病毒FM1 非结构蛋白1 黏病毒抗性蛋白A Janus激酶/信号转导与转录激活因子信号 

分 类 号：R285.5[医药卫生—中药学]