馥感啉口服液通过TGF-β1/Smad3信号通路改善肥胖哮喘小鼠气道重塑  

Fuganlin oral liquid ameliorates airway remodeling through TGF-β1/Smad3 signaling pathway in asthmatic mice

作　　者：李小英 郭健敏 张文强 戴锦龙 杨威 江涛 LI Xiao-ying;GUO Jian-min;ZHANG Wen-qiang;DAI Jin-long;YANG Wei;JIANG Tao(School of Guangdong Pharmaceutical University,Guangzhou 510006,China;Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd.,Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research,Non-clinical Evaluation Sub-center for Traditional Chinese Medicine of National Engineering Research Center for Modernization of Traditional Chinese Medicine,Guangdong Engineering Research Center for Innovative Drug Evaluation and Research,Guangzhou 510990,China)

机构地区：[1]广东药科大学中药学院,广东广州510006 [2]广东莱恩医药研究院有限公司,广东省药物非临床评价研究企业重点实验室,国家中药现代化工程技术研究中心中药非临床评价分中心,广东省创新药物评价与研究工程技术研究中心,广东广州510990

出　　处：《中国药理学通报》2022年第4期619-625,共7页Chinese Pharmacological Bulletin

基　　金：国家重大新药创制(No 2018ZX09721003-009-025);广东省药物非临床评价研究企业重点实验室(No 2018B030323024);广东省重点领域研发计划“新药创制”重点专项(No 2019B020202001)。

摘　　要：目的探讨馥感啉对肥胖哮喘小鼠气道重塑的影响及其作用机制。方法高脂饲料喂养联合OVA诱导建立C57 BL/6肥胖哮喘慢性气道炎症模型,经灌胃馥感啉5.86、11.72、23.44 g·kg^(-1)治疗,末次激发后采用肺功能震荡仪检测呼吸系统阻力(Rrs)、呼吸系统弹性(Ers)、呼吸系统顺应性(Crs);测定白细胞总数;HE及Masson染色观察肺组织病理改变;ELISA法检测IgE及肺组织、TGF-β1、Smad3、SP水平;IHC检测肺组织Smad3、SARA蛋白表达。结果馥感啉抑制小鼠血液中白细胞数量的增加,降低血清中IgE含量;减轻Rrs,和Ers增强,调节呼吸功能。病理结果显示,馥感啉能减轻肥胖哮喘模型炎性细胞浸润和胶原沉积,抑制支气管粘膜增生;ELISA结果显示,小鼠肺组织TGF-β1、Smad3、SP的含量降低;IHC结果表明,馥感啉抑制了肺组织Smad3、SARA蛋白表达量。结论馥感啉抗肥胖型哮喘作用可能通过改善呼吸功能、控制气道炎症,拮抗气道重塑相关。Aim To explore the effect of Fuganlin on airway remodeling in obese asthmatic mice and its mechanism.Methods A model of chronic airway inflammation in C57 BL/6 mice with obese asthma induced by OVA and high-fat diet was established,and treated with Fuganlin 5.86,11.72 and 23.44 g·kg^(-1) by gavage.After the last challenge,the respiratory system resistance(Rrs),respiratory system elasticity(Ers),and respiratory system compliance(Crs)were measured with a lung function oscillator;the total number of white blood cells in whole blood was measured;tissue HE and MASSON staining were employed to observe the pathological changes.ELISA was used to detect the levels of IgE in serum and the levels of TGF-β1,Smad3 and SP in lung tissues;IHC was used to detect the expression levels of Smad3,SARA and protein in lung tissues.Results Fuganlin reduced the increase in the number of white blood cells in blood and inhibited the content of IgE in serum.Fuganlin could reduce the Rrs and Ers,enhance the Crs and regulate the respiratory function.Histopathological results showed that Fuganlin could reduce inflammatory cell infiltration and collagen deposition in the chronic airway inflammation model of obese mice,and inhibit bronchial mucosal proliferation;ELISA results showed that Fuganlin inhibited the expression of TGF-β1,Smad3,and SP;IHC results showed that Smad3 and SARA protein expression decreased.Conclusions The anti-obesity asthma effect of Fuganlin may help to improve respiratory function,control airway inflammation,and antagonize airway remodeling.

关 键 词：馥感啉口服液 肥胖哮喘 TGF-β1/Smad3 气道重塑 SARA 气道高反应性 

分 类 号：R-332[医药卫生] R282.71