α-亚麻酸对哮喘大鼠模型气道炎症和FGF23表达的影响  

Effects of Alpha-linolenic acid on airway inflammation and fibroblast growth factor 23 expression in rat model of asthma

作　　者：任引刚 张莹 白莉敏 高砚丽 祝松涛 REN Yingang;ZHANG Ying;BAI Limin;GAO Yanli;ZHU Songtao(Department of Geriatrics,The Second Affiliated Hospital of Air Force Medical University,Xi′an 710038,China)

机构地区：[1]空军军医大学第二附属医院老年医学科,陕西西安710038

出　　处：《西部医学》2023年第10期1418-1424,1432,共8页Medical Journal of West China

基　　金：陕西省重点研发计划项目(2019SF-202)。

摘　　要：目的探讨α-亚麻酸对哮喘大鼠模型气道炎症和成纤维细胞生长因子23(FGF23)表达的影响。方法选取50只SPF级雄性SD大鼠建立卵白蛋白(OVA)诱导的哮喘SD大鼠模型,将大鼠随机分为对照组、OVA组(哮喘模型大鼠)、OVA+40 mg/kg ALA组(采用40 mg/kg的α-亚麻酸治疗哮喘模型大鼠)、OVA+80 mg/kg ALA组(采用80 mg/kg的α-亚麻酸治疗哮喘模型大鼠)和OVA+Dex组(采用0.25 mg/kg的地塞米松治疗哮喘模型大鼠),每组10只。各组大鼠均连续治疗处理7 d。通过HE染色评价肺组织形态。通过ELISA法检测支气管肺泡灌洗液(BALF)中干扰素-γ(IFN-γ)、白细胞介素(IL)-4、IL-17和IL-10的水平。采用自动生化分析仪检测各组大鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)。通过免疫组化、Western blot或qRT-PCR检测肺组织FGF23、FGFR4、Klotho、E-cadherin和α-SMA的表达。结果与OVA组相比,OVA+40 mg/kg ALA组、OVA+80 mg/kg ALA组和OVA+Dex组大鼠肺组织病变均明显减轻。与OVA组相比,OVA+40 mg/kg ALA组、OVA+80 mg/kg ALA组和OVA+Dex组大鼠BALF中IFN-γ和IL-10的水平升高,而IL-4和IL-17降低(均P<0.05)。与OVA组相比,OVA+40 mg/kg ALA组、OVA+80 mg/kg ALA组和OVA+Dex组大鼠血清中TC、TG和LDL水平降低,而HDL升高(均P<0.05)。与OVA组相比,OVA+40 mg/kg ALA组、OVA+80 mg/kg ALA组和OVA+Dex组大鼠肺组织E-cadherin的蛋白表达水平升高,而α-SMA降低(均P<0.05)。与OVA组相比,OVA+40 mg/kg ALA组、OVA+80 mg/kg ALA组和OVA+Dex组大鼠肺组织FGF23和FGFR4的mRNA和蛋白表达水平降低,而Klotho水平升高(均P<0.05)。结论α-亚麻酸可抑制哮喘大鼠的气道炎症和上皮-间充质转化、改善脂代谢,其机制可能是通过纠正Th1/Th2和Treg/Th17的失衡及调节FGF23-Klotho-FGFR4信号来实现的。Objective This study aimed to reveal the effect ofα-linolenic acid on airway inflammation and fibroblast growth factor 23(FGF23)expression in rats model of asthma.Methods In this study,an ovalbumin(OVA)-induced asthma SD rat model was established,and the rats were randomly divided into 5 groups(n=10):control group,OVA group(asthma model rats),OVA+40 mg/kg ALA group(asthmatic model rats treated with 40 mg/kgα-linolenic acid),OVA+80 mg/kg ALA group(asthmatic model rats treated with 80 mg/kgα-linolenic acid)and OVA+Dex group(asthmatic model rats treated with 0.25 mg/kg dexamethasone).The rats were treated continuously for 7 days.Lung tissue morphology was evaluated by HE staining.The levels of interferon-γ(IFN-γ),interleukin(IL)-4,IL-17 and IL-10 in bronchoalveolar lavage fluid(BALF)were detected by ELISA.Serum total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL)and high-density lipoprotein(HDL)were detected by automatic biochemical analyzer.The expressions of FGF23,FGFR4,Klotho,E-cadherin andα-SMA in lung tissue were detected by immunohistochemistry,Western blot or qRT-PCR.Results Compared with OVA group,OVA+40 mg/kg ALA group,OVA+80 mg/kg ALA group and OVA+Dex group rats had significantly reduced lung lesions.Compared with OVA group,the levels of IFN-γand IL-10 in the BALF of OVA+40 mg/kg ALA group,OVA+80 mg/kg ALA group and OVA+Dex group were increased,while the levels of IL-4 and IL-17 decreased(P<0.05).Compared with OVA group,the serum levels of TC,TG and LDL in OVA+40 mg/kg ALA group,OVA+80 mg/kg ALA group and OVA+Dex group were decreased,while HDL was increased(P<0.05).Compared with OVA group,the protein expression level of E-cadherin in the lung tissue of OVA+40 mg/kg ALA group,OVA+80 mg/kg ALA group and OVA+Dex group increased,whileα-SMA decreased(P<0.05).Compared with OVA group,the mRNA and protein expression levels of FGF23 and FGFR4 in the lung tissue of OVA+40 mg/kg ALA group,OVA+80 mg/kg ALA group and OVA+Dex group were decreased,while Klotho level was increased(P<0.05).Conclusio

关 键 词：Α-亚麻酸 哮喘 气道炎症 上皮-间充质转化 脂代谢 FGF23-Klotho-FGFR4信号 

分 类 号：R562.25[医药卫生—呼吸系统]