哮喘小鼠气道血管生成及其机制的实验研究  

Study on the airway angiogenesis and its mechanisms in mouse models of asthma

作　　者：郭志福[1] 李强[1] 姚小鹏[1] 马凌云[1] 白冲[1] 

机构地区：[1]第二军医大学长海医院呼吸内科,上海200433

出　　处：《中国呼吸与危重监护杂志》2005年第2期106-109,共4页Chinese Journal of Respiratory and Critical Care Medicine

摘　　要：目的　观察急性、慢性哮喘小鼠气道血管生成的变化 ,探讨其机制。方法　 2 4只BALB/c小鼠随机分为 3组 ,每组 8只 ,即正常对照组、急性哮喘组和慢性哮喘组。通过卵白蛋白(OVA)多次腹腔注射致敏和反复滴鼻激发 ,建立急性、慢性哮喘小鼠模型。末次激发后 2 4h处死动物 ,右肺行灌洗留取支气管肺泡灌洗液 (BALF) ,左肺和气管制备病理切片。病理切片行HE染色和抗Ⅷ因子免疫组织化学染色 ,显微镜下计数气管黏膜固有层、黏膜下层血管密度。ELISA法检测BALF中白细胞介素 4 (IL- 4 )、干扰素 -γ(IFN -γ)、血管内皮生长因子 (VEGF)及内皮抑素含量。结果(1 )急性哮喘组气道血管密度无明显变化 ;慢性哮喘组气道血管密度明显高于正常对照组 (P <0 . 0 1 )。 (2 )急性、慢性哮喘组BALF中IL 4浓度均明显高于正常对照组 (P值均 <0 .0 1 ) ,慢性哮喘组低于急性哮喘组 (P <0 .0 1 ) ;急性哮喘组IFN -γ浓度明显低于正常对照组 (P <0 . 0 1 ) ,慢性哮喘组与正常对照组无显著性差异 ;急性、慢性哮喘组IL -4 /IFN -γ比值均明显高于正常对照组 (P值均 <0 . 0 1 ) ,慢性哮喘组明显低于急性哮喘组 (P <0 . 0 5 )。 (3)急性、慢性哮喘组BALF中VEGF和内皮抑素浓度均明显高于正常对照组 (P值均 <0 .0 1 ) ,急性、慢性哮喘组间?Objective To observe the airway angiogenesis and elucidate its mechanisms in asthmatic mouse models.Methods Asthmatic mouse models were established by sensitized and challenged with allergen (OVA) in which chronic asthma model was repeatedly challenged with OVA for 76 days.Pathological slides were prepared from left lungs and tracheae and stained with hematoxylin-eosin.Anti-Factor ⅧAg antibody was used to detect vessels.The number of vessels in lamina propria and submucosa of tracheae was counted microscopically.Concentrations of IL-4,IFN-γ,VEGF,and endostatin in BALF from right lungs were detected by ELISA.ResultsThere was no significant difference in the density of vessels between the normal control mice and acute asthmatic mice,however,the density increased significantly in chronic asthmatic mouse group compared with that in the normal control and the acute asthmatic mouse group(both P<0.01).The concentration of IL-4 in BALF was increased significantly in chronic and acute asthmatic group (both P<0.01).There was a significant increase of IFN-γ in BALF of acute asthmatic mouse group but not in chronic group.The ratio of IL-4 to IFN-γ was increased in chronic and acute asthmatic mouse group (both P<0.01),but it was higher in chronic asthmatic mouse group than that in acute asthmatic mouse group (P<0.05).There was significant increases of VEGF and endostatin in BALF in chronic and acute asthmatic mouse group (both P<0.01) with no significant difference between acute and chronic asthma groups.The ratio of VEGF to endostatin was significant increased in chronic but not acute asthmatic mouse group (P<0.01).Conclusions The airway angiogenesis is prominent in chronic not in asthmatic mice.The airway angiogenesis in chronic asthmatic mice might be related to the imbalance between Th1- and Th2-type cytokines and the imbalance between angiogenic and antiangiogenic factors in airway.

关 键 词：慢性哮喘 急性哮喘 正常 气道 对照组 血管生成 小鼠 BALF IL-4 IFN-Γ 

分 类 号：R562.25[医药卫生—呼吸系统] R725.622.5[医药卫生—内科学]