Department of Critical Care Medicine, The Second Hospital of Shandong University, Jinan, Shandong, China (mainland).
Department of Critical Care Medicine, The Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China (mainland).
Med Sci Monit. 2019 Sep 28;25:7295-7305. doi: 10.12659/MSM.917037.
BACKGROUND Penehyclidine hydrochloride is a novel drug for acute respiratory distress syndrome. The aim of the study was to reveal the impact of smoking on the efficacy of the drug in rats with acute respiratory distress syndrome. MATERIAL AND METHODS A 132 Sprague-Dawley rats were used in this study; 72 rats were used in the smoking models. Penehyclidine hydrochloride (3 mg/kg) was injected to induce acute respiratory distress syndrome. Rats were divided into the smoking group and the non-smoking group; these 2 groups were subdivided according to different treatments. The arterial blood gas analysis (PaO₂/FiO₂) and extent of pneumonedema (wet-to-dry weight ratio) was analyzed to evaluate disease severity. Expressions of mitogen-activated protein kinases (p-p38MAPK, p38MAPK, p-ERK, ERK, p-JNK, and JNK) in lung tissue were measured using western blot assay. RESULTS Penehyclidine hydrochloride improved the pneumonedema (wet-to-dry weight ratio) and hyoxemia (PaO₂/FiO₂) of the disease in non-smoking group (P<0.001, P<0.001 respectively), but not in smoking group (P=0.244, P=0.424 respectively). The drug inhibited the expressions of phospho-p38MAPK and phospho-ERK in non-smoking group (P<0.001, P<0.001 respectively), but not in smoking group (P=0.350, P=0.507 respectively). In the smoking group, blocking the phospho-p38MAPK or phospho-ERK signal pathway by their inhibitors showed a better therapeutic effect on the pneumonedema and hyoxemia compared with the use of penehyclidine hydrochloride (phospho-p38MAPK: P=0.004, P=0.010 respectively; phospho-ERK: P=0.022, P=0.004 respectively). CONCLUSIONS The study confirmed the protective effect of penehyclidine hydrochloride in acute respiratory distress syndrome, mainly in the non-smoking group, which might be explained by the fact that phospho-p38MAPK and phospho-ERK signal pathways were difficult to inhibit by the drug in the smoking group.
盐酸戊乙奎醚是一种新型急性呼吸窘迫综合征药物。本研究旨在揭示吸烟对急性呼吸窘迫综合征大鼠药物疗效的影响。
本研究使用了 132 只 Sprague-Dawley 大鼠；其中 72 只用于建立吸烟模型。注射盐酸戊乙奎醚（3mg/kg）诱导急性呼吸窘迫综合征。大鼠分为吸烟组和非吸烟组；这两组根据不同的治疗方案进一步分为亚组。分析动脉血气分析（PaO₂/FiO₂）和肺水肿程度（湿干重比）以评估疾病严重程度。采用 Western blot 法检测肺组织中丝裂原活化蛋白激酶（p-p38MAPK、p38MAPK、p-ERK、ERK、p-JNK 和 JNK）的表达。
盐酸戊乙奎醚可改善非吸烟组疾病的肺水肿（湿干重比）和低氧血症（PaO₂/FiO₂）（P<0.001，P<0.001），但对吸烟组无明显作用（P=0.244，P=0.424）。药物抑制非吸烟组磷酸化 p38MAPK 和磷酸化 ERK 的表达（P<0.001，P<0.001），但对吸烟组无明显作用（P=0.350，P=0.507）。在吸烟组中，用其抑制剂阻断磷酸化 p38MAPK 或磷酸化 ERK 信号通路可改善肺水肿和低氧血症，与使用盐酸戊乙奎醚相比，疗效更好（磷酸化 p38MAPK：P=0.004，P=0.010；磷酸化 ERK：P=0.022，P=0.004）。
本研究证实了盐酸戊乙奎醚在急性呼吸窘迫综合征中的保护作用，主要在非吸烟组，这可能是由于吸烟组中药物难以抑制磷酸化 p38MAPK 和磷酸化 ERK 信号通路所致。
