利多卡因对失血性休克大鼠肺损伤的保护作用

Effects of lidocaine on adhesion molecules expression in lung injury after ischemic shock in rats

目的 探讨利多卡因对失血性休克大鼠肺损伤的保护作用。方法 80只雄性Wistar大鼠建立失血性休克模型后,随机分为四组,假手术组(Ⅰ组,n=8)、休克组(Ⅱ组,n=8)、生理盐水组(Ⅲ组,n=32)、利多卡因组(Ⅳ组,n=32)。Ⅰ组于假手术后,Ⅱ组于休克60 min,Ⅲ、Ⅳ组分别于复苏开始后2、4、8、12 h,测定中性粒细胞(PMNs)表面粘附分子CD11b/CD18表达、肺组织中髓过氧化物酶(MPO)活性,并采用光镜和透射电镜观察肺组织的病理学改变。结果 与Ⅰ组比较,Ⅲ组、Ⅳ组复苏后各时点PMNs表面CD11b/CD18表达均升高(P<0.01),Ⅱ组差异无显著性(P>0.01),Ⅱ组、Ⅲ组、Ⅳ组复苏后各时点肺组织中MPO活性升高(P<0.05或0.01)。与Ⅲ组比较,Ⅳ组复苏后同一时点、Ⅰ组、Ⅱ组PMNs表面CD11b/CD18表达及肺组织中MPO活性降低(P<0.01)。结论 小剂量利多卡因可以抑制失血性休克大鼠PMNs表面CD11b/CD18的表达,减少PMNs在肺组织中的浸润,从而减轻肺损伤。

Objective To study the effect of lidocaine on the expression of CD11b/CD18 and MPO in lung injury after hemorrhagic shock in rats. Methods Eighty male Wistar rats weighing 230-270 g were randomly divided into 4 groups: sham operation group ( group Ⅰ, n = 8 ) received operation without shock, shock group ( group Ⅱ, n = 8 ) received hemorrhagic shock without resuscitation , normal saline treatment group (group Ⅲ, n = 32 ) received normal saline after shock, lidocaine treatment group ( group Ⅳ, n = 32 ) received lidocaine after shock. The animals were anesthetized with intraperitoneal pentobarbital sodium 40 mg· kg-1 . Hemorrhagic shock was induced by withdrawing blood from right femoral artery at the rate of 2.0 ml·kg-1· min-1 , MAP was maintained at 40 mm Hg for 60 min before resuscitation. Direct arterial MAP and HR were continuously monitored. Group Ⅳwas received lidoacaine at the beginning of resuscitation with a bonus dose 2.0 mg· kg-1 and then followed continuous infusion1.0mg·kg-1·h-1 for 2 h. Group III was received the same dose of normal saline. Flow cytometric analysis was used to assess the expression of CD11b/CD18 on leukocyte and the change of myeloperoxidase (MPO) in the lung was studied at the end of shock (groupⅡ ) and at 2,4, 8, 12 h after resuscitation (group Ⅲ, group Ⅳ) . The rats were sacrificed and the piece of lung was immediately removed for electron microscopic examination. Result In group Ⅲand group Ⅳ ,the expression of CD11b/CD18 on PMNs and MPO in lung were increased significantly compared with Group Ⅰ. Microscopic examination indicated the longer time of reperfusion ,the more serious injury of the lung. And in groupⅣ ,the changes of CD11b/CD18 and MPO were reduced as compared with group Ⅲ (P < 0.01), the lung injury was also ameliorated. Conclusion Lidocaine can inhibit the expression of adhesion molecules, consequently lung injury after ischemic shock is attenuated.