基于IGF-1R/PI3K/AKT的益气固表丸对慢性阻塞性肺疾病模型大鼠的影响及作用机制研究

Effects and Mechanism of Yiqi Gubiao Pills on Chronic Obstructive Pulmonary Disease in Model Rats Based on IGF-1R/PI3K/AKT Signaling Pathway

目的:益气固表丸对慢性阻塞性肺疾病(COPD)有明显的治疗作用,但具体作用机制尚不清楚。本研究旨在探讨益气固表丸对脂多糖(LPS)联合烟雾暴露构建慢性阻塞性肺病模型大鼠的治疗作用机制。方法:通过大鼠气管内灌注LPS和吸入香烟烟雾构建慢性阻塞性肺病模型,同时给予模型大鼠低、中、高剂量益气固表丸治疗14 d。观察呼吸参数及肺组织病理变化。采用酶联免疫吸附试验测定支气管肺泡灌洗液(BALF)及血清胰岛素样生长因子1型受体(IGF-1R)、白细胞介素-1β(IL-1β)、IL-10水平。采用蛋白质印迹法检测大鼠肺组织样品中胰岛素样生长因子1受体(IGF-1R)/PI3K/AKT信号通路组分的磷酸化状态。结果:与对照组和低剂量益气组比较,大剂量益气固表丸治疗可显著改善COPD大鼠呼吸参数,减轻肺损伤和炎症,降低BALF和血清炎症介质水平。此外,高剂量益气固表丸干预的COPD大鼠肺组织标本中磷酸化IGF-1R、p-PI3K、p-AKT、p-GSK3、p-mTOR蛋白水平显著降低。结论:益气固表丸对COPD有明显的治疗作用,可能与靶向IGF-1R/PI3K/AKT信号通路有关。

Objective:Yiqi Gubiao Pills have a definite therapeutic effect on chronic obstructive pulmonary disease(COPD),but the specific mechanism of action remains unclear.This study aimed to explore the therapeutic mechanism of Yiqi Gubiao Pills in the treatment of COPD in rats induced by lipopolysaccharide(LPS) combined with cigarette smoke exposure.Methods:The COPD model was induced in rats by intratracheal instillation of LPS and cigarette smoke inhalation.Meanwhile, the model rats were treated with low-,medium-,or high-dose Yiqi Gubiao Pills for 14 days.The respiratory parameters and pulmonary histopathological changes were examined.The enzyme-linked immunosorbent assay(ELISA) was conducted to measure the levels of insulin-like growth factor 1 receptor(IGF-1R),interleukin(IL)-1β,and IL-10 in bronchoalveolar lavage fluid(BALF) and serum.Western blot was used to determine the phosphorylation of the components in the IGF-1R/PI3K/AKT signaling pathway in the lung tissues of rats.Results:Compared with the control group and the low-dose Yiqi Gubiao Pills group, the high-dose Yiqi Gubiao Pills group showed significantly improved respiratory parameters, alleviated lung injury and inflammation, and reduced proinflammatory cytokine levels in BALF and serum of COPD rats.Furthermore, high-dose Yiqi Gubiao Pills could significantly reduce the protein levels of phosphorylated(p)-IGF-1R,p-PI3K,p-AKT,p-GSK3,and p-mTOR in the lung tissues of COPD rats.Conclusion:Yiqi Gubiao Pills have a definite therapeutic effect on COPD,and the mechanism may be related to targeting the IGF-1R/PI3K/AKT signaling pathway.