欧前胡素通过TGF-β1/Smad3和PI3K/Akt信号通路对哮喘小鼠气道重塑模型的影响  

Effects of imperatorin on airway remodeling in asthmatic mice through TGF-β1/Smad3 and PI3K/Akt signaling pathways

作　　者：咸哲民 王重阳 朴玉华 李俊峰 姜京植 赵雨喆 李良昌 朴红梅 延光海 XIAN Zhe-min;WANG Chong-yang;PIAO Yu-hua;LI Jun-feng;JIANG Jing-zhi;ZHAO Yu-zhe;LI Liang-chang;PIAO Hong-mei;YAN Guang-hai(Respiratory Medicine Dept,Affiliated Hospital;Dept of Anatomy,School of Basic Medical Sciences,Yanbian University,Yanji Jilin 133002,China)

机构地区：[1]延边大学附属医院呼吸内科,吉林延吉133002 [2]延边大学医学院解剖学教研室,吉林延吉133002

出　　处：《中国药理学通报》2018年第12期1719-1724,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81660003;81560679)

摘　　要：目的探究欧前胡素(imperatorin, IMP)对哮喘小鼠气道重塑模型的抑制作用,其机制是否与TGF-β1/Smad3和PI3K/Akt信号通路相关。方法将40只♀BALB/c小鼠随机分成5组,即正常对照组、OVA气道重塑模型组、欧前胡素治疗组(30、60 mg·kg^(-1))、地塞米松阳性对照组(1 mg·kg^(-1))。使用HE、Masson染色法检查小鼠肺组织病理学变化;Diff-Quick染色对小鼠BALF中的总细胞和嗜酸性粒细胞(eosinophilia, EOS)进行计数;ELISA方法检测IL-4、IL-5、IL-13、IgE、TGF-β1的含量;免疫组织化学法检测肺组织中α-平滑肌肌动蛋白(α-SMA)的表达水平;Western blot对肺组织中α-SMA、MMP-9、TGF-β1、p-Smad3、p-Akt的含量进行定量分析。结果欧前胡素减少胶原沉积和炎症细胞渗出;欧前胡素抑制IL-4、IL-5、IL-13、IgE、TGF-β1和EOS的生成;免疫组化结果显示,欧前胡素可减少肺组织中α-SMA的阳性面积;Western blot结果显示,欧前胡素抑制α-SMA、MMP-9、TGF-β1、Smad3和Akt的蛋白表达量。结论欧前胡素通过TGF-β1/Smad3和PI3K/Akt通路对OVA诱导的哮喘小鼠气道重塑模型起到抑制作用。Aim To explore the inhibitory effect of imperatorin（IMP） on airway remodeling model of asthmatic mice, and whether its mechanism is related to TGF-β1/Smad3 and PI3K/Akt signaling pathways. Methods Forty female BALB/c mice were randomly divided into five groups, namely control group, OVA airway remodeling model group, IMP treatment group（30 and 60 mg·kg ^-1 were used respectively）, Dex positive control group（1 mg·kg ^-1 ）. HE and Masson staining were used to observe the lung histopathological changes in mice; diff-quick staining was applied to count the total cells and EOS in BALF; ELISA was used to detect the contents of IL-4, IL-5, IL-13, IgE, TGF-β1; immunohistochemical method was used to detect the expression levels of α-SMA in lung tissues; Western blot was employed to quantitatively assess the contents of α-SMA, MMP-9, TGF-β1, p-Smad3, p-Akt in lung tissues. Results IMP reduced collagen deposition and the exudation of inflammatory cells; IMP inhibited the generation of EOS and TGF-β1; the results of immunohistochemical indicated that IMP increased the expression of α-SMA in lung tissues; the results of Western blot showed that IMP inhibited the protein expression of α-SMA, MMP-9, TGF-β1, Smad3 and Akt. Conclusions IMP has inhibitory effect on the OVA-induced airway remodeling mouse model through TGF-β1/Smad3 and PI3K/Akt pathways.

关 键 词：欧前胡素 气道重塑 转化生长因子β1 磷脂酰肌醇-3激酶 Α-平滑肌肌动蛋白 基质金属蛋白酶9 

分 类 号：R-332[医药卫生] R284.1