异丙酚对失血性休克／复苏兔胃黏膜细胞凋亡的影响

Effects of propofol on gastric mucosal cellular apoptosis after resuscitation of hemorrhagic shock in rabbits

目的评价异丙酚对失血性休克／复苏兔胃黏膜细胞凋亡的影响。方法健康成年雄性新西兰大白兔100只，体重2．5，3．0kg，采用随机数字表法，将其随机分为5组（n=20）：假手术组（S组）、模型组（M组）及异丙酚不同给药时机组P1组：预先给药组、P2组：后处理组和P3组：治疗组。采用股动脉放血及股静脉回输血、输液法制备失血性休克／复苏诱发胃黏膜损伤模型，MAP降至35～40mmHg并维持60min。P1组、P2组和P3组分别于放血前10min、复苏开始前10min及复苏开始后20min时静脉注射异丙酚5rag／kg后，以20mg·kg-1～·h-1静脉输注至复苏开始后90min，S组和M组给予等容量生理盐水。复苏开始后90min时取胃组织，肉眼下观察胃黏膜损伤情况，采用TUNEL法和免疫组化法分别测定胃黏膜细胞凋亡及Bcl-2和Bax蛋白表达。结果与S组比较，余4组胃黏膜有不同程度损伤，凋亡指数（AI）及Bax蛋白表达升高，而Bcl-2蛋白表达及Bcl-2／Bax比值降低（P〈0．05或0．01）。与M组比较，P1组、P2组和P3组胃黏膜损伤减轻，AI降低，Pl组和P2组Bax蛋白表达降低，而Bcl-2蛋白表达和Bcl-2／Bax比值升高（P〈0．05或0．01）。与B组比较，P1组胃黏膜损伤减轻，AI和Bax蛋白表达降低，而Bcl-2蛋白表达和Bcl-2／Bax比值升高（P〈0．05）。结论异丙酚预先给药和后处理通过上调Bcl-2蛋白表达和下调Bax蛋白表达减轻失血性休克／复苏兔胃黏膜细胞凋亡。

Objective To investigate the effects of propofol on gastric mucosal cellular apoptosis after resuscitation of hemorrhagic shock in rabbits. Methods One hundred healthy adult male New Zealand rabbits weighing 2.5-3.0 kg were randomly divided into 5 groups （ n = 20 each） ： group sham operation （group S） ; group hemorrhagic shock （group M） and III, IV, V 3 propofol groups （groups P1,2,3）. Hemorrhagic shock was induced by withdrawing blood from femoral artery. MAP was reduced to 35-40 mm Hg and maintained at this level for 60 min in groups M, P1, P2 and P3- Blood was then traodused back via femoral vein to restore blood vohtme. In groups PI.2,3 propofol 5 mg/kg was injected iv at 10 rain before ischemia （group P1 ）, 10 min before （group P2） and 20 min of resuscitation （ group P3 ） respectively followed by continuous infusion at 20 mg·kg- 1·h-1 until 90 min of re- suscitation. The gastric mucous membrane specimens were obtained at 90 min of resuseitation for macroscopic examination and detection of apoptosis （by TUNEL） and Bcl-2 and Bax protein expression （by immuno-histochemis- try）. Results Hemorrhagic shock seriously damaged gastric mucous membrane, significantly increased apoptotie index （the number of apoptotic cells/the total number of cells） and Bax protein expression and decreased Bel-2 protein expression and Bcl-2/Bax ratio in group M as compared with group S. Propofol significantly attenuaied hemorragic shock-induced above changes in groups P1 and P2 . Conclusion Pre- and post-conditioning with propofol can attenuate apoptosis in gastric mucous membrane cells induced by hemorrhagic shock by up-regulating Bcl-2 protein expression and down-regulating Bax protein expression.