槲皮素基于EGFR信号通路减轻大鼠气道黏液高分泌  

Quercetin reduces airway mucus hypersecretion in rats based on EGFR signaling pathway

作　　者：邬勋平 陶禹至 刘琳 韩婧(指导)[1,3] 刘维佳 WU Xunping;TAO Yuzhi;LIU Lin;HAN Jing;LIU Weijia(Guizhou University School of Medicine,Guiyang 550025,China)

机构地区：[1]贵州大学医学院,贵阳550025 [2]遵义医科大学,遵义563000 [3]贵州省人民医院呼吸与危重症医学科,贵阳550002

出　　处：《中国免疫学杂志》2022年第8期940-945,共6页Chinese Journal of Immunology

基　　金：贵州省人民医院博士基金项目(GZSYBS[2018]08号)。

摘　　要：目的:探讨槲皮素对LPS诱导的大鼠气道黏液高分泌的作用及其分子机制。方法:将36只SD大鼠随机分为:对照组、LPS组、槲皮素低、中、高剂量组、AG1478组;气道内滴注LPS建立大鼠气道黏液高分泌模型。HE染色观察肺组织的病理变化;AB-PAS染色观察杯状细胞增生和黏液分泌情况;ELISA检测肺组织中MUC5AC浓度;采用免疫组织化学法(IHC)检测MUC5AC、EGFR、PKC、NF-κB表达;RT-qPCR检测肺组织MUC5AC及EGFR mRNA表达;Western blot检测p-EGFR、EGFR、p-PI3K、PI3K、p-PKC、PKC、p-AKT、AKT、NF-κB表达。结果:与LPS组相比,槲皮素低、中、高剂量组病理变化逐渐减轻,肺组织炎症积分和AB-PAS阳性着色面积逐渐降低(P<0.05);槲皮素能减少肺组织MUC5AC、EGFR、PKC、NF-κB表达,降低MUC5AC含量,并下调MUC5AC及EGFR的mRNA水平(P<0.05);槲皮素能减少p-EGFR/EGFR、p-PI3K/PI3K、p-PKC/PKC、p-AKT/AKT、NF-κB蛋白表达(P<0.05)。结论:气管内滴注LPS能成功诱导大鼠气道黏液高分泌模型,槲皮素对LPS诱导大鼠气道黏液高分泌具有拮抗作用,其作用机制可能与抑制EGFR信号通路,调控p-EGFR/EGFR、p-PI3K/PI3K、p-PKC/PKC、p-AKT/AKT、NF-κB表达,下调MUC5AC表达有关。Objective:To explore the effect and molecular mechanism of quercetin on LPS-induced airway mucus hypersecretion in rats.Methods:Thirty-six SD rats were randomly divided into Control group,LPS group,different doses of quercetin low,medium and high group,AG1478 group;rats were instilled LPS into the airway to establish the model of airway mucus hypersecretion.HE staining was used to observe pathological changes in lung tissue;AB-PAS staining was used to observe goblet cell proliferation and mucus secretion;MUC5AC of lung tissue was detect by ELISA;expressions of MUC5AC,EGFR,PKC and NF-κB were detected by immunohistochemistry(IHC);mRNA expressions of MUC5AC and EGFR were detected by RT-qPCR;protein expressions of p-EGFR,EGFR,p-PI3K,PI3K,p-PKC,PKC,p-AKT,AKT,NF-κB were detected by Western blot.Results:Compared with the LPS group,pathological changes of the quercetin low,medium and high dose groups were gradually reduced,and the lung tissue inflammation score and the AB-PAS positive staining area gradually decreased(P<0.05);quercetin could reduce the expressions of MUC5AC,EGFR,PKC and NF-κB in lung tissues,reduce the content of MUC5AC,and down-regulate the mRNA levels of MUC5AC and EGFR(P<0.05);quercetin could reduce the expressions of p-EGFR/EGFR,p-PI3K/PI3K,p-PKC/PKC,p-AKT/AKT,NF-κB(P<0.05).Conclusion:Intratracheal instillation of LPS can successfully induce airway mucus hypersecretion in rats.Quercetin has an antagonistic effect on LPS-induced airway mucus hypersecretion in rats.Its mechanism may be related to the inhibition of EGFR signaling pathway,regulate the expressions of p-EGFR/EGFR,p-PI3K/PI3K,p-PKC/PKC,p-AKT/AKT,NF-κB,there by down-regulating the expression of MUC5AC.

关 键 词：槲皮素 气道 黏液高分泌 MUC5AC EGFR 

分 类 号：R285.5[医药卫生—中药学]