中药新药与临床药理2025，Vol.36Issue(12)：2062-2071,10.DOI:10.19378/j.issn.1003-9783.2025.12.006
肺康颗粒基于TLR-Hippo/MST信号轴调控慢性阻塞性肺疾病大鼠肺泡巨噬细胞骨架的相关机制
The Mechanism of Feikang Granules in Regulating the Cytoskeleton of Alveolar Macrophages in Chronic Obstructive Pulmonary Disease Rats via the TLR-Hippo/MST Signaling Axis
摘要
Abstract
Objective To investigate the mechanism of Feikang Granules in regulating the cytoskeleton of alveolar macrophages in rats with chronic obstructive pulmonary disease(COPD)based on the TLR-Hippo/MST signaling axis.Methods(1)Cell experiment:A stable-staged COPD rat model was established.Alveolar macrophages(AM)were isolated from the rats and divided into the control group,the COPD group,the control+MST inhibitor(XMU-MP-1)group,and the COPD+MST inhibitor group for intervention.Protein expression levels of Toll-like receptor 4(TLR4),mammalian STE20-like protein kinase 1/2(MST1/2),Rac1,and p-Rac1 in AMs were detected by Western Blot.mRNA levels of TLR4,MST1/2,and Rac1 were measured by RT-qPCR.Changes in cytoskeleton were observed under a fluorescence microscope.(2)Animal experiment:A stable-staged COPD rat model was established and divided into the control group,the COPD group,the MST inhibitor group,the dexamethasone group,and the low-,medium-,and high-dose Feikang Granules groups for intervention.Protein expression levels of TLR4,MST1/2,Rac1,and p-Rac1 in AMs were detected by Western Blot.mRNA levels of TLR4,MST1/2,and Rac1 were measured by RT-qPCR.Cytoskeletal structural changes after Feikang Granules intervention were observed under a fluorescence microscope.Protein expression of TLR4,MST1/2,and p-Rac1 in lung tissues was observed by immunohistochemistry.Pathological changes in lung tissue sections were examined microscopically after hematoxylin and eosin(HE)staining.Results(1)Cell experiment:Compared with the control group,the COPD group and the control+MST inhibitor group showed significantly increased p-Rac1 protein expression(P＜0.05,P＜0.01),significantly decreased protein expression of TLR4,MST1/2,and Rac1(P＜0.05,P＜0.01),decreased mRNA expression levels of TLR4,MST1/2,and Rac1(P＜0.05),and incomplete morphology of alveolar macrophages.(2)Animal experiment:Compared with the control group,the COPD group and the MST inhibitor group showed significantly increased p-Rac1 protein expression(P＜0.01),significantly decreased protein expression of TLR4,MST1/2,and Rac1(P＜0.01),decreased mRNA expression levels of TLR4,MST1/2,and Rac1(P＜0.05),and incomplete alveolar macrophage morphology.Compared with the COPD group,the low-,medium-,and high-dose Feikang Granules groups showed significantly increased protein expression of TLR4,MST1/2,and Rac1(P＜0.05,P＜0.01),increased mRNA expression of TLR4,MST1/2,and Rac1(P＜0.05),and partial restoration of alveolar macrophage morphology.Compared with the control group,the COPD group and the MST inhibitor group showed decreased protein expression of TLR4 and MST1/2 in lung tissue(P＜0.05),increased p-Rac1 protein expression(P＜0.01),thinned alveolar walls,and disrupted alveolar structure.Compared with the COPD group,the low-,medium-,and high-dose Feikang Granules groups showed significantly decreased p-Rac1 protein expression in lung tissue(P＜0.05,P＜0.01),significantly increased protein expression of TLR4 and MST1/2(P＜0.05),and varying degrees of restoration in alveolar structure.Conclusion COPD rats exhibit low expression of TLR4,MST1/2,and Rac1,inhibition of the TLR-Hippo/MST signaling axis,and abnormal cytoskeleton in alveolar macrophages.Feikang Granules can improve the cytoskeleton of alveolar macrophages by modulating the TLR-Hippo/MST signaling axis.关键词
肺康颗粒/培土生金法/慢性阻塞性肺疾病/TLR-Hippo/MST信号轴/细胞骨架/大鼠/巨噬细胞Key words
Feikang Granules/banking up earth for generating metal method/chronic obstructive pulmonary disease/TLR-Hippo/MST signaling axis/cytoskeleton/rats/macrophages分类
医药卫生引用本文复制引用
麦杰茗,杨柳柳,张雨露,周若伊,王浩洁..肺康颗粒基于TLR-Hippo/MST信号轴调控慢性阻塞性肺疾病大鼠肺泡巨噬细胞骨架的相关机制[J].中药新药与临床药理,2025,36(12):2062-2071,10.基金项目
国家自然科学基金项目(82474411,81904132) （82474411,81904132）
广州地区中医药重大科技项目(2025QN008). （2025QN008）
