戊乙奎醚对肢体缺血再灌注诱发大鼠肺损伤的影响

Effects of penehyclidine hydrochloride on lung injury induced by lower limb ischemia-reperfusion in rats

目的探讨戊乙奎醚对肢体缺血再灌注诱发大鼠肺损伤的影响。方法雄性Wistar大鼠36只，体重250～300g，随机分为4组（n=9）：对照组（Ⅰ组）、肢体缺血再灌注诱发肺损伤组（Ⅱ组）、小剂量盐酸戊乙奎醚组（Ⅲ组）和大剂量盐酸戊乙奎醚组（Ⅳ组）。Ⅱ组、Ⅲ组和Ⅳ组麻醉后双后肢缺血3h，Ⅲ组和Ⅳ组分别于股动脉开放前10min肌肉注射盐酸戊乙奎醚2、9mg／kg，再灌注4h快速取肺，计算肺组织湿／干重比（W／D），透射电镜下观察肺组织超微结构，酶联免疫吸附法测定肺组织肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-10含量。结果与Ⅰ组比较，Ⅱ组肺组织W／D及TNF-α、IL-10含量升高（P〈0．01）；与Ⅱ组比较，Ⅲ组肺组织W／D及TNF-α含量降低、IL-10含量升高（P〈0．01）；与Ⅲ组比较，Ⅳ组肺组织W／D及TNna含量降低、IL-10含量升高（P〈0．01）。结论戊乙奎醚可减轻肢体缺血再灌注诱发大鼠肺损伤，且呈剂量依赖性，其机制与降低肺组织炎性反应有关。

Objective To investigate the effects of different doses of penehyclidine HCl on lung injury induced by lower limb ischemia-reperfusion （I/R） in rats and the underlying mechanism. Methods Thirty-six male Wistar rats weighing 250-300 g were randomly divided into 4 groups （ n = 9 each） ： group Ⅰ control; group Ⅱ lower limb I/R; group Ⅲ penehycfidine HCI 2 mg/kg and group Ⅳ penehyclidine HCl 9 mg/kg. The animals were anesthetized with intraperitoneal 4 % chloral hydrate 10 ml/kg, and bilateral femoral arteries were clamped for 3 h in group Ⅱ , Ⅲ and Ⅳ . In group Ⅲ and Ⅳ penehyclidine HCl 2 mg/kg and 9 mg/kg were injected IM at 10 min before femoral A unclamping respectively. The animals were sacrificed and the lungs were removed at 4 h of reperfusion. The W/D lung weight ratio was determined and the uhrastructural changes were observed with transmission electron microscope （TEM）. TNF-α and IL-10 content in the lung tissue were determined by enzymelinked immunosorbent assay （ELISA）. Results Lower limb I/R significantly increased W/D lung weight ratio and lung TNF-α content and decreased lung IL-10 content and the lung uhrastructure was badly damaged in group Ⅱ. Penehyclidine HCl administration significantly attenuated I/R-induced changes in a dose-dependent manner in group Ⅲ and Ⅳ. Conclusion Penehyclidine HCl can attenuate lung injury induced by lower limb I/R in a dose- dependent manner by inhibition of inflammatory response.