Kuzubova N A, Lebedeva E S, Fedin A N, Dvorakovskaya I V, Titova O N
Institute of Pulmonology, I. P. Pavlov St. Petersburg State Medical University; I. P. Pavlov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
Bull Exp Biol Med. 2013 Jun;155(2):214-7. doi: 10.1007/s10517-013-2116-2.
We studied the effect of a non-steroidal anti-inflammatory drug fenspiride on contractive activity of bronchial smooth muscles on the model of chronic obstructive pulmonary disease of rats induced by 60-day exposure to nitrogen dioxide. The administration of fenspiride during the acute stage of the disease (day 15) abolished the constricting effect of the pollutant on the bronchial smooth muscles. Dilatation effect of fenspiride in a low dose (0.15 mg/kg) was mediated by its interaction with nerve endings of bronchial capsaicin-sensitive nerve C-fibers. The interaction of drug with receptors of C-fibers prevented neurogenic inflammation, which was confirmed by the absence of structural changes in the lungs typical of this pathology. The broncholytic effect of fenspiride in a high dose (15 mg/kg) was mediated by not only afferent pathways, but also its direct relaxing action on smooth muscle cells. The observed anti-inflammatory and bronchodilatation effect of fenspiride in very low doses can be used for prevention of chronic obstructive pulmonary disease in risk-group patients contacting with aggressive environmental factors.
我们研究了非甾体抗炎药喷司哌啶对二氧化氮暴露60天诱导的大鼠慢性阻塞性肺疾病模型中支气管平滑肌收缩活性的影响。在疾病急性期(第15天)给予喷司哌啶可消除污染物对支气管平滑肌的收缩作用。低剂量(0.15mg/kg)喷司哌啶的舒张作用是通过其与支气管辣椒素敏感神经C纤维神经末梢的相互作用介导的。药物与C纤维受体的相互作用可预防神经源性炎症,这一点通过肺部无该病理典型的结构变化得到证实。高剂量(15mg/kg)喷司哌啶的支气管舒张作用不仅由传入途径介导,还由其对平滑肌细胞的直接舒张作用介导。在极低剂量下观察到的喷司哌啶的抗炎和支气管扩张作用可用于预防接触侵袭性环境因素的高危组患者的慢性阻塞性肺疾病。