目的 探讨肺康颗粒基于 TLR-Hippo/MST 信号轴调控慢性阻塞性肺疾病（COPD，慢阻肺）大鼠肺泡巨噬 细胞骨架的相关机制。方法 （1）细胞实验：制备慢阻肺大鼠稳定期动物模型，分离大鼠的肺泡巨噬细胞 （AM），分为对照组、慢阻肺组、对照 MST 抑制剂（XMU-MP-1）组及慢阻肺 MST 抑制剂组并进行干预。利用 Western Blot 法检测各组肺泡巨噬细胞中 Toll 样受体 4（TLR4）、哺乳动物 STE20 样蛋白激酶（MST）1/2、Rac1、 p-Rac1 蛋白表达，RT-qPCR 法检测各组肺泡巨噬细胞中 TLR4、MST1/2、Rac1 mRNA 的变化，荧光显微镜下 观察细胞骨架结构变化；（2）动物实验：制备慢阻肺大鼠稳定期动物模型，分为对照组、慢阻肺组、MST 抑制 剂组、地塞米松组及肺康颗粒低、中、高剂量组并进行干预，利用 Western Blot 法检测各组肺泡巨噬细胞中 TLR4、MST1/2、Rac1、p-Rac1 蛋白表达，RT-qPCR 法检测各组肺泡巨噬细胞中 TLR4、MST1/2、Rac1 mRNA 的变化，荧光显微镜下观察肺康颗粒干预后细胞骨架结构变化，免疫组织化学技术观察各组肺组织 TLR4、 MST1/2、p-Rac1 蛋白表达的变化，显微镜下观察苏木素伊红染色肺组织病理切片。结果 （1）细胞实验：与对 照组比较，慢阻肺组和对照 MST 抑制剂组 p-Rac1 蛋白表达明显升高（P＜0.05，P＜0.01），TLR4、MST1/2、 Rac1 蛋白表达明显下降（P＜0.05，P＜0.01），TLR4、MST1/2、Rac1 mRNA 表达水平下降（P＜0.05），肺泡巨 噬细胞形态不完整。（2）动物实验：与对照组比较，慢阻肺组和 MST 抑制剂组 p-Rac1 蛋白表达明显升高（P＜ 0.01），TLR4、MST1/2、Rac1 蛋白表达明显下降（P＜0.01），TLR4、MST1/2 、Rac1 mRNA 表达水平下降（P＜ 0.05），肺泡巨噬细胞形态不完整；与慢阻肺组比较，肺康颗粒低、中、高剂量组 TLR4、MST1/2、Rac1 蛋白 表达明显升高（P＜0.05，P＜0.01），TLR4、MST1/2、Rac1 mRNA 表达升高（P＜0.05），肺泡巨噬细胞形态有所 恢复。与对照组大鼠比较，慢阻肺组以及 MST 抑制剂组大鼠肺脏组织中 TLR4、MST1/2 蛋白的表达量下降 （P＜0.05），p-Rac1 蛋白表达量升高（P＜0.01），大鼠肺泡壁变薄，肺泡结构破坏；与慢阻肺组比较，肺康颗 粒低、中、高剂量组大鼠肺脏组织 p-Rac1 蛋白表达明显下降（P＜0.05，P＜0.01），同时 TLR4、MST1/2 蛋白 表达明显上升（P＜0.05），肺组织肺泡结构有不同程度恢复。结论 慢阻肺大鼠 TLR4、MST1/2、Rac1 呈低表 达状态，TLR-Hippo/MST 信号轴被抑制，同时肺泡巨噬细胞存在骨架结构异常。肺康颗粒可通过调控 TLR- Hippo/MST 信号轴改善慢阻肺肺泡巨噬细胞骨架结构。

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.

R285.5

国家自然科学基金项目（82474411，81904132）；广州地区中医药重大科技项目（2025QN008)。