基于Rac1信号通路研究淫羊藿苷对慢性阻塞性肺疾病模型小鼠肺泡巨噬细胞胞葬及吞噬功能的影响

目的 探讨淫羊藿苷基于Rac1信号通路改善慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）模型小鼠肺泡巨噬细胞胞葬及吞噬功能障碍的作用机制。方法 40只C57BL/6小鼠随机分为空白组、模型组、Rac1抑制剂（2.5 mg/kg）组和淫羊藿苷低、高剂量（40、80 mg/kg）组，每组8只，除空白组外其余各组小鼠采用香烟烟雾熏吸8周的方法制备COPD模型，造模后ip Rac1抑制剂或ig淫羊藿苷，1次/d，每周给药6次，连续4周。检测小鼠体质量、肺功能指标；ELISA法检测肺组织中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-4(interleukin-4,IL-4)、IL-6、乳脂球表皮生长因子8(milk fat globule EGF factor 8,MFG-E8)和生长停滞特异性蛋白6(growth arrest specific protein 6,GAS6)含量；流式细胞术检测肺泡巨噬细胞胞葬及吞噬能力、小鼠全血巨噬细胞M1/M2分型；苏木素-伊红染色（hematoxyl...

Effect of icariin on improving efferocytosis and phagocytosis dysfunction of alveolar macrophages in chronic obstructive pulmonary disease model mice based on Rac1 signaling pathway

Objective To investigate the mechanism of icariin in improving efferocytosis and phagocytosis dysfunction of alveolar macrophages in chronic obstructive pulmonary disease (COPD) model mice based on Rac1 signaling pathway. Methods A total of 40 C57BL/6 mice were randomly divided into blank group, model group, Rac1 inhibitor (2.5 mg/kg) group, icariin low- and high-dose (40, 80 mg/kg) groups, with eight mice in each group, except for the blank group, the rest groups of mice were prepared by cigarette smoke inhalation for eight weeks to prepare a mouse COPD model. After modeling, rats were ip Rac1 inhibitor or icariin, once a day, six times a week for four consecutive weeks. Body weight and lung function indices were detected; ELISA was used to detect levels of tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, milk fat globule EGF factor 8 (MFG-E8) and growth arrest specific protein 6 (GAS6) in lung tissue; Flow cytometry was used to detect the efferocytosis and phagocytosis function of alveolar macrophages, and the M1/M2 phenotype of whole blood macrophages in mice; HE staining was used to observe the pathological changes of lung tissue, as well as mean linear intercept (MLI) and mean alveolar numbers (MAN); qRT-PCR and Western blotting were used to detect Rac1, P21 activated kinase (PAK) mRNA and protein expressions in lung tissue; Macrophage phagocytosis and structural changes of skeleton were observed by laser confocal microscopy. Results Compared with blank group, body weight, lung function indexes, phagocytosis and efferocytosis function of mice in model group were decreased (P < 0.05, 0.01), MLI was increased (P < 0.01), MAN was decreased (P < 0.01), inflammatory factors IL-4, IL-6 and TNF-α levels in lung tissue were increased (P < 0.05, 0.01), levels of efferocytosis cofactors MFG-E8 and GAS6 were decreased (P < 0.05), M1-type macrophages was increased (P < 0.05), Rac1, PAK mRNA and protein expressions in lung tissue were up-regulated (P < 0.05, 0.01). Compared with model group, lung function indexes were improved after the intervention with Rac1 inhibitor and icariin (P < 0.05, 0.01), phagocytosis and efferocytosis function were improved (P < 0.05, 0.01), levels of inflammatory factors were decreased (P < 0.05, 0.01), levels of efferocytosis cofactors were increased (P < 0.05), M2 type macrophages were increased (P < 0.05, 0.01), Rac1, PAK mRNA and protein expressions in lung tissue were decreased (P < 0.05, 0.01). Conclusion Icariin can modulate the Rac1 signaling pathway to mediate macrophage skeleton rearrangement and improve phagocytosis and efferocytosis dysfunction of alveolar macrophages in COPD mice.