和厚朴酚对慢性哮喘模型大鼠气道炎症及气道重塑的抑制作用及其机制  

Inhibitory effect of honokiol on airway inflammation and remodeling in chronic asthmatic rats and its potential mechanism

作　　者：南李刚[1] 王贵佐[2] 杨淑梅[2] 刘璐 NAN Ligang;WANG Guizuo;YANG Shumei;LIU Lu(Department of Emergency,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;Department of Respiratory and Critical Care Medicine,Shaanxi Provincial People’s Hospital)

机构地区：[1]陕西省人民医院急诊科,西安710068 [2]陕西省人民医院呼吸与危重症一科

出　　处：《山西医科大学学报》2023年第9期1231-1236,共6页Journal of Shanxi Medical University

基　　金：国家自然科学基金青年基金项目(82000037);陕西省重点研发计划重点产业创新链(群)项目(2020ZDLSF01-06);陕西省人民医院科技人才支持计划项目(2021JY-10)。

摘　　要：目的探讨和厚朴酚对慢性哮喘模型大鼠气道炎症和气道重塑的影响及其可能机制。方法24只雄性SD大鼠随机分为4组(每组各6只):对照组、卵清蛋白(ovalbumin,OVA)模型组、和厚朴酚组以及地塞米松组。OVA模型组第1,7,14天腹腔注射新鲜配制OVA混悬液致敏,第21天起接受1%OVA溶液雾化吸入30 min/次,隔日1次,共雾化8周。对照组PBS代替OVA腹腔注射及雾化吸入;和厚朴酚组和地塞米松组每次OVA雾化前1 h分别腹腔注射和厚朴酚溶液(5 mg/kg)和地塞米松(0.5 mg/kg)。末次激发后24 h处死大鼠,观察各组大鼠肺组织病理变化;收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)进行炎性细胞计数及分类;ELISA法检测血清及BALF中IL-4、IL-6、IL-17含量;免疫印迹法检测肺组织Yes相关蛋白(Yes-associated protein,YAP)水平变化。结果与对照组相比,OVA模型组支气管管壁、平滑肌层增厚,气道及血管周围大量炎性细胞浸润;BALF炎性细胞总数、嗜酸性粒细胞及中性粒细胞数显著增加(P<0.01),BALF中IL-4、IL-6、IL-17水平显著增高(P<0.01),大鼠肺组织内YAP表达增多(P<0.01)。与OVA模型组相比,和厚朴酚组及地塞米松组大鼠肺组织病理改变明显减轻,BAFL中炎性细胞总数、嗜酸性粒细胞及中性粒细胞数显著减少(P<0.01),IL-4、IL-6、IL-17水平降低(P<0.01),而和厚朴酚组与地塞米松组间上述改变相似;与OVA模型组相比,和厚朴酚组大鼠肺组织内YAP表达减少(P<0.01)。结论和厚朴酚可以抑制慢性哮喘模型大鼠气道炎症和气道重塑,推测其作用机制可能与和厚朴酚下调YAP表达有关。Objective To investigate the effect of honokiol(HKL)on airway inflammation and remodeling in chronic asthmatic rats and its possible mechanism.Methods Twenty-four SD male rats were randomly divided into four groups evenly and randomly:control group,ovalbumin(OVA)model group,HKL+OVA group and dexamethasone(Dex)+OVA group.In OVA model group,rats were initially sensitized by intraperitoneal injection of OVA suspension at day 1,7 and 14,and then the rats were exposed to the inhalation of 1%OVA for 30 min on alternate days for 8 weeks.The rats in control group received PBS instead of OVA.In HKL+OVA group and Dex+OVA group,the rats were intraperitoneally injected with HKL(5 mg/kg)and Dex(5 mg/kg)at 1 h before OVA challenge,respectively.At 24 h after the last excitation,the rats were sacrificed.The pathological changes of lung tissues were observed.The numbers of total inflammatory cells,eosinophils and neutrophils in bronchoalveolar lavage fluid(BALF)in each group were counted.The concentrations of IL-4,IL-6 and IL-17 in serum and BALF were detected by ELISA.The protein level of YAP in lung tissues was measured by immunoblotting.Results Compared with control group,bronchial wall and airway smooth muscle layer were thickened,more inflammatory cells were clustered around blood vessels and airways.Compared with control group,the numbers of total inflammatory cells,eosinophils and neutrophils in BALF,and the concentrations of IL-4,IL-6 and IL-17 in serum and BALF were all increased(P<0.01),and the level of YAP protein was upregulated in OVA model group(P<0.01).Compared with OVA model group,the pathological changes of lung tissues were improved,the numbers of inflammatory cells in BALF were decreased in HKL+OVA group and Dex+OVA group(P<0.01),and the concentrations of inflammatory factors in serum and BALF were decreased(P<0.01),and the above indicators were similar between HKL+OVA group and Dex+OVA group.Compared with OVA model group,the protein level of YAP in lung tissues was decreased in HKL+OVA group(P<0.01).Conclusion

关 键 词：和厚朴酚 哮喘 气道炎症 气道重塑 YAP 

分 类 号：R562.2[医药卫生—呼吸系统]