小檗碱改善流感病毒性肺炎小鼠肺血管通透性的作用及机制  

The Improving Effect and Mechanism of Berberine on Lung Vascular Permeability of Mice with Viral Pneumonia Caused by Influenza Virus

作　　者：吴莹[1] 李季倩[1] 孟建 路广林[1] 郝钰[1] 

机构地区：[1]北京中医药大学医学病原系,北京100029 [2]北京市王府中西医结合医院,北京102209

出　　处：《现代生物医学进展》2012年第17期3205-3208,3270,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(30772871);北京中医药大学创新团队"经方现代应用关键科学问题的基础研究"项目(2011-CXD-04)

摘　　要：目的:观察小檗碱对流感病毒感染所致病毒性肺炎小鼠肺血管通透性的影响,并探讨其作用机制。方法:BALB/c小鼠108只随机分为3组,正常组、模型组、小檗碱组,25μL 50LD50病毒液滴鼻建立流感病毒感染的小鼠肺炎模型,感染后1 h,正常组和模型组予以双蒸水灌胃,小檗碱组予药物0.005 g.kg-1d-1腹腔注射;各组均给药2次/d,连续给药5 d。感染后的2 d、4 d、6 d,处死小鼠,肺组织称重以检测肺含水量;1%伊文氏兰5 mL/kg尾静脉注射检测肺血管通透性;Bicinchoninic acid(BCA)法检测肺泡灌洗液(BALF)中蛋白含量;放免法或酶免法测定肺组织中PGE2、PLA2及LT-B4含量。结果:病毒感染后,模型组肺含水量持续升高,肺血管通透性及BALF蛋白含量在感染后第4天开始明显升高,小檗碱降低了肺含水量、肺血管通透性及BALF蛋白含量(P<0.01);模型组肺组织中PGE2、PLA2、LT-B4的含量明显升高,小檗碱不同程度地抑制了PGE2、PLA2、LT-B4的表达。结论:小檗碱通过抑制流感病毒感染后肺组织中PGE2、PLA2、LT-B4的释放,降低了肺血管通透性及肺含水量,对病毒性肺炎中肺水肿的形成,起到一定的治疗作用。Objective： To investigate the effect and the mechanism of berberine on lung vascular permeability of mice with viral pneumonia caused by influenza virus.Methods： All BALB/c mice（n=108） were randomly divided into 3 groups： control group,model group,and berberine group.25μl 50 LD50 influenza virus,mouse lung-adapted strain,was intranasally inoculated to mice except the control group.1 h after the infection,mice in control and model group were intragastrically given 25μl distilled water for day 5;Mice in berberine group were treated by intraperitoneal injection with berberine at a dose of 0.005 g·kg-1d-1 by day 5.On days 2,4 and 6 after infection,mice were killed and the lungs were extracted.The lung tissues were weighed to detect the lung water content;1% Evans blue with the final concentration as 5 mL/kg was intravenously injected to detect lung vascular permeability;Radioimmunoassay and ELISA were used to detect the concentration of prostaglandin E2（PGE2）,phospholipase A2（PLA2）,and leukotriene（LTB4）,respectively.Results： The lung water content in model group increased continuously,and the lung vascular permeability and the protein content of BALF increased in model group from day 4.Berberine obviously decreased lung water content,lung vascular permeability and the protein content of BALF（P〈0.01）.The concentration of PGE2,PLA2 and LTB4 was significantly higher in model group,and berberine inhibited the expression of PGE2,PLA2 and LTB4 in different extent.Conclusion： Berberine decreased lung vascular permeability and lung water content by inhibiting the production of inflammatory mediators PGE2,PLA2 and LTB4,which suggests that berberine has therapeutic effects on pulmonary edema in viral pneumonia.

关 键 词：小檗碱 病毒性肺炎 流感病毒 炎性介质 肺血管通透性 

分 类 号：Q953[生物学—动物学] R563.14[医药卫生—呼吸系统]