格隆溴铵对高氧诱导幼鼠急性肺损伤的影响及其机制研究

Effects and mechanisms of glycopyrronium bromide on hyperoxia-induced acute lung injury in young rats

摘要:

目的 探究格隆溴铵对高氧诱导幼鼠急性肺损伤（ALI）的影响及作用机制。方法 从30只SD幼鼠中随机选取10只为对照组，其余幼鼠成功复制高氧诱导的ALI模型，随机分为ALI组、格隆溴铵组，每组10只。格隆溴铵组雾化吸入0.8 mg/（kg·d）格隆溴铵，ALI组、对照组吸入等体积生理盐水，连续给药7 d后，测量幼鼠肺组织湿/干重比值（W/D）、肺指数，检测白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）及肿瘤坏死因子-α（TNF-α）水平及血清活性氧基团（ROS）、超氧化物歧化酶（SOD）水平，比较肺组织病理学变化及Toll样受体4/髓分化因子88（TLR4/MyD88）通路蛋白的表达。结果 与对照组比较，ALI组W/D及肺指数升高（P <0.05），血清IL-1β、IL-6、TNF-α、SOD水平升高（P <0.05），ROS水平降低（P <0.05），TLR4、MyD88蛋白相对表达量上调（P <0.05）；与ALI组比较，格隆溴铵组W/D及肺指数降低（P <0.05），血清IL-1β、IL-6、TNF-α、SOD水平降低（P <0.05），ROS水平升高（P <0.05），TLR4、MyD88蛋白相对表达量下调（P <0.05）。结论 格隆溴铵能改善血清炎症指标及氧化应激指标，降低高氧诱导的ALI，其作用机制可能与TLR4/MyD88通路有关。

Abstract:

Objective To explore the effects and mechanisms of glycopyrronium bromide on hyperoxia-induced acute lung injury (ALI) in young rats.Methods Ten out of thirty SD young rats were randomly selected as the control group, while the rest of the rats were successfully established as hyperoxia-induced ALI models, which were further randomly divided into the ALI group and the glycopyrronium bromide group, with 10 rats in each group. The rats in the glycopyrronium bromide group were given glycopyrronium bromide at a dose of 0.8 mg/(kg·d) via inhalation, while rats in the ALI group and the control group were administered with an equal volume of normal saline. After continuous administration for 7 days, the lung wet-to-dry weight ratio (W/D) and lung index of the young rats were measured. The serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) and superoxide dismutase (SOD) were detected. The pathological changes of lung tissues and the expressions of proteins associated with the Toll-like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88) pathway were compared.Results Compared with the control group, the lung W/D and the lung index were increased, serum levels of IL-1β, IL-6, TNF-α and SOD were elevated, the level of ROS was decreased, and the relative protein expressions of TLR4 and MyD88 were up-regulated in the ALI group (P < 0.05). Compared with the ALI group, the lung W/D and the lung index were decreased, serum levels of IL-1β, IL-6, TNF-α and SOD were lowered, the level of ROS was increased, and the relative protein expressions of TLR4 and MyD88 were down-regulated in the glycopyrronium bromide group (P < 0.05).Conclusions Glycopyrronium bromide can improve serum inflammatory and oxidative stress indicators, and mitigate the hyperoxia-induced ALI, the mechanism of which may be related to the TLR4/MyD88 pathway.