Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People's Republic of China.
Department of Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2021 Mar 31;16:877-885. doi: 10.2147/COPD.S295329. eCollection 2021.
Penehyclidine hydrochloride is a selective antagonist of M1 and M3 receptors. Clinical studies suggest that it is a potential drug for the treatment of chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate the effect of penehyclidine hydrochloride on the inflammatory response of lung tissue during mechanical ventilation in rats with COPD and explore the role of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signaling pathway.
Eight-week-old male Sprague Dawley rats were exposed to cigarette smoke for 30 minutes every day for two months, and on the first and thirtieth days, 200 ug of lipopolysaccharide was injected into the trachea. Two months later, the rats were randomly divided into the control group (C), model group (M), model + normal saline group (N), and penehyclidine hydrochloride group (H) to undergo anesthesia and mechanical ventilation. In group H, 1 mg/kg of penehyclidine hydrochloride was injected intravenously.
The results showed that: ① Compared with group C, the other groups all showed typical chronic obstructive pathological changes in the lung tissue; their wet/dry weight ratio (W/D), TNF-α, JNK, and p-JNK levels increased (P < 0.05), and their interleukin (IL)-10 levels decreased (P < 0.05). ② Compared with group M, there was no significant change in the lung tissue indexes in group N (P > 0.05). ③ Compared with group N, the W/D, TNF-α, JNK, and p-JNK levels in group H decreased (P < 0.05), while the levels of IL-10 increased (P < 0.05).
Penehyclidine hydrochloride can alleviate the pulmonary inflammatory response in rats with COPD undergoing mechanical ventilation. The JNK/SAPK signaling pathway may be involved in this process.
盐酸戊乙奎醚是 M1 和 M3 受体的选择性拮抗剂。临床研究表明，它是一种治疗慢性阻塞性肺疾病（COPD）的潜在药物。本研究旨在评估盐酸戊乙奎醚对 COPD 大鼠机械通气时肺组织炎症反应的影响，并探讨 c-Jun N-末端激酶/应激激活蛋白激酶（JNK/SAPK）信号通路的作用。
将 8 周龄雄性 Sprague Dawley 大鼠每天暴露于香烟烟雾 30 分钟，持续两个月，并在第 1 天和第 30 天向气管内注射 200 μg 脂多糖。两个月后，大鼠随机分为对照组（C）、模型组（M）、模型+生理盐水组（N）和盐酸戊乙奎醚组（H），进行麻醉和机械通气。在 H 组中，静脉注射 1mg/kg 的盐酸戊乙奎醚。
结果显示：①与 C 组相比，其他组的肺组织均表现出典型的慢性阻塞性病理改变；其湿/干重比（W/D）、TNF-α、JNK 和 p-JNK 水平升高（P<0.05），白细胞介素（IL）-10 水平降低（P<0.05）。②与 M 组相比，N 组的肺组织指标无明显变化（P>0.05）。③与 N 组相比，H 组的 W/D、TNF-α、JNK 和 p-JNK 水平降低（P<0.05），而 IL-10 水平升高（P<0.05）。
盐酸戊乙奎醚可减轻 COPD 大鼠机械通气时的肺部炎症反应，JNK/SAPK 信号通路可能参与这一过程。
