丙泊酚调控巨噬细胞极化对支气管哮喘小鼠气道炎症反应和Toll样受体4-NOD样受体蛋白3通路的影响  

Effect of propofol regulating macrophage polarization on airway inflammatory response and Toll-like receptor 4-NOD-like receptor protein 3 pathway in mice with bronchial asthma

作　　者：邵忠新[1] 李世英[2] SHAO Zhongxin;LI Shiying(Department of Anesthesiology,Zhongshan Hospital Affiliated to Xiamen University,Xiamen,Fujian,361004;Department of Surgical Anesthesiology,Zhongshan Hospital Affiliated to Xiamen University,Xiamen,Fujian,361004)

机构地区：[1]厦门大学附属中山医院麻醉科,福建厦门361004 [2]厦门大学附属中山医院手术麻醉科,福建厦门361004

出　　处：《实用临床医药杂志》2025年第6期13-19,共7页Journal of Clinical Medicine in Practice

基　　金：福建医学科技青年培育项目(21FBQN1921006)。

摘　　要：目的探讨丙泊酚(Pro)调控巨噬细胞极化对支气管哮喘(BA)小鼠气道炎症反应和Toll样受体4-NOD样受体蛋白3(TLR4-NLRP3)通路的影响。方法将40只BA造模小鼠随机分为BA组、Pro低剂量(Pro-L)组、Pro高剂量(Pro-H)组、Pro-H+脂多糖(LPS)组,每组10只。另取10只正常小鼠作为Control组。检测各组小鼠肺功能[最大呼气流量(PEF)、每分钟通气量(VE)],肺泡灌洗液中嗜酸性粒细胞(EOS)、淋巴细胞(LYM)和中性粒细胞(NEU)数量,白细胞介素(IL)-4、IL-10、IL-5和IL-13水平;采用流式细胞术检测外周血巨噬细胞M1型和M2型水平,辅助性T细胞(Th)1和Th2细胞比例;采用酶联免疫吸附测定(ELISA)检测血清γ干扰素(IFN-γ)、免疫球蛋白E(IgE)水平;采用苏木精-伊红(HE)染色观察肺组织病理形态;采用Western blot检测肺组织中cleaved caspase-3、TLR4、NLRP3和Caspase-1蛋白表达。结果与Control组比较,BA组小鼠肺组织有明显损伤,PEF、VE、IL-10、巨噬细胞M1型、Th1细胞比例、IFN-γ水平降低,EOS、LYM、NEU数量以及IL-4、IL-5、IL-13、巨噬细胞M2型水平、Th2细胞比例、IgE、cleaved caspase-3、TLR4、NLRP3和Caspase-1蛋白表达水平升高,差异有统计学意义(P<0.05);与BA组相比,Pro-L组、Pro-H组小鼠肺组织有明显损伤,PEF、VE、IL-10、巨噬细胞M1型水平、Th1细胞比例、IFN-γ水平升高,EOS、LYM、NEU数量以及IL-4、IL-5、IL-13水平、巨噬细胞M2型水平、Th2细胞比例、IgE、cleaved caspase-3、TLR4、NLRP3和Caspase-1蛋白表达水平降低,差异有统计学意义(P<0.05);LPS可显著减弱Pro对BA小鼠的改善作用(P<0.05)。结论Pro可能通过抑制TLR4-NLRP3信号通路来调节BA小鼠巨噬细胞极化和免疫反应,降低炎症反应程度,改善肺组织形态和肺功能。Objective To investigate the effect of propofol(Pro)regulating macrophage polarization on airway inflammatory response and Toll-like receptor 4-NOD-like receptor protein 3(TLR4-NLRP3)pathway in mice with bronchial asthma(BA).Methods Forty BA model mice were randomly divided into BA group,low-dose Pro(Pro-L)group,high-dose Pro(Pro-H)group,and Pro-H+lipopolysaccharide(LPS)group,with 10 mice in each group.Additionally,10 normal mice were included as control group.Lung function indicators[peak expiratory flow(PEF)and ventilation volume(VE)],eosinophil(EOS),lymphocyte(LYM)and neutrophil(NEU)counts in bronchoalveolar lavage fluid,and interleukin(IL)-4,IL-10,IL-5 and IL-13 levels were measured in each group;flow cytometry was used to detect M1 and M2 macrophage levels and the proportions of T helper(Th)1 and Th2 cells in peripheral blood;the enzyme-linked immunosorbent assay(ELISA)was used to detect serum interferon-γ(IFN-γ)and immunoglobulin E(IgE)levels;the hematoxylin-eosin(HE)staining was used to observe the pathological morphology of lung tissues;the Western blot was used to detect the protein expression of cleaved caspase-3,TLR4,NLRP3 and Caspase-1 in lung tissues.Results Compared with the control group,mice in the BA group showed significant lung tissue damage,decreased PEF,VE,IL-10 and M1 macrophage levels,Th1 cell proportion,and IFN-γlevel,and significant increased EOS,LYM,NEU counts,IL-4,IL-5,IL-13 and M2 macrophage levels,Th2 cell proportion,IgE,cleaved caspase-3,TLR4,NLRP3,and Caspase-1 protein expression levels(P<0.05).Compared with the BA group,mice in the Pro-L and Pro-H groups showed significant lung tissue damage,increased PEF,VE,IL-10 and M1 macrophage levels,Th1 cell proportion,and IFN-γlevel,and significant decreased EOS,LYM,NEU counts,IL-4,IL-5,IL-13 and M2 macrophage levels,Th2 cell proportion,IgE,cleaved caspase-3,TLR4,NLRP3,and Caspase-1 protein expression levels(P<0.05).LPS significantly attenuated the improvement effect of Pro in BA mice(P<0.05).Conclusion Pro may regulate macrophage polari

关 键 词：丙泊酚 巨噬细胞 支气管哮喘 TOLL样受体4 NOD样受体蛋白3 辅助性T细胞 炎症反应 组织病理学 

分 类 号：R965[医药卫生—药理学] R562.2[医药卫生—药学] Q591[生物学—生物化学]