异丙酚对兔创伤失血性休克复苏胃黏膜损伤的影响

Effects of propofol on gastric mucosal injury by traumatic hemorrhagic shock resuscitation in rabbits

目的探讨异丙酚对兔创伤失血性休克复苏胃黏膜损伤(trauma hemorrhagic shock resuscitation-gastric mucosal injury,THSR-GMI)核因子κB(nuclear factor-κB,NF-κB)表达及其炎性反应和细胞凋亡的影响,以明确异丙酚对THSR-GMI的作用及机制。方法成年新西兰雄性大白兔75只,随机分为对照组(S组)、模型组(M组)以及失血前应用异丙酚组(P1组)、复苏前应用异丙酚组(P2组)和复苏后应用异丙酚组(P3组)各15只。建立THSR-GMI模型。P1组、P2组及P3组分别于失血前10 min、复苏前10 min及复苏20 min时静脉注射异丙酚5 mg/kg后,以20 mg·kg^-1·h^-1速度持续静脉泵注,S组和M组给予等容量生理盐水。复苏90 min时取静脉血及胃组织标本,肉眼下观察胃黏膜损伤程度,放大镜下计算胃黏膜损伤指数(damage index,DI)及光镜下计数中性粒细胞(polymorphonuclear leukocyte,PMN),采用末端脱氧核苷酰基转移酶介导性dUTP切口末端标记(terminal deoxynucleatidyl transferase-mediated dUTPincision end labeling,TUNEL)法和免疫组织化学技术分别测定胃黏膜细胞凋亡指数(apoptotic index,AI)和NF-κB表达,以酶联免疫吸附测定法测定血清肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素6(interleukin-6,IL-6)浓度。结果与S组比,M组、P1组、P2组和P3组胃黏膜出现不同程度损伤,其DI值、PMN计数、AI值、NF-κB表达以及血清TNF-α和IL-6浓度均升高(P<0.05);与M组比,P1组、P2组和P3组的胃黏膜损伤不同程度减轻,其DI值、PMN计数、AI值、NF-κB表达以及血清TNF-α和IL-6浓度均降低(P<0.05)。与P3组比,P1组的胃黏膜损伤减轻,其DI值、PMN计数、AI值、NF-κB表达以及血清TNF-α和IL-6浓度均降低(P<0.05)。结论异丙酚可通过下调NF-κB表达,抑制炎性反应和细胞凋亡,从而减轻兔THSR-GMI,以失血前应用效果较佳。

Objective To investigate the effects of propofol on the expression of nuclear factor-κB(NF-κB)and the inflammatory response and apoptosis in the traumatic hemorrhagic shock resuscitation-gastric mucosal injury(THSR-GMI)in rabbits,and to clarify the effects of propofol on THSR-GMI.Methods Seventy-five New Zealand healthy adult male rabbits were randomly divided into 5 groups,15 rabbits in each group:control group(group S),model group(group M),pro-ischemia group(group P1),pro-resuscitation group(group P2)and post-resuscitation group(group P3).The traumatic hemorrage resuscitation-gastric mucosal injury model was established.In group P1,group P2 and group P3,propofol 5mg/kg was injected intravenously 10 min before ischemia,resuscitation and 20 min at resuscitation repectively,then propofol 20 mg·kg^-1·h^-1 was infused.In group S and group M,propofol was replaced with equal volume of normal saline.After 90 minutes of resuscitation,the venous blood and gastric tissue samples were taken,and the degree of gastric mucosa injury was observed with naked eyes.The damage index(DI)of gastric mucosa was calculated under magnifying glass,and the polymorphonuclear leukocyte(PMN)were counted under light microscope.The expression of apoptosis index(AI)and NF-κB in gastric mucosa were measured by terminal deoxynucleotidyl transferase-mediated dUTPincision end labeling(TUNEL)and immunohistochemistry,respectively.Serum tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were measured by enzyme linked immunosorbent assay concentration.Results Compared with group S,the gastric mucosa were damaged in different degrees,and the DI,PMN counts,AI and the expression of NF-κB in the gastric mucosa,and the serum levels of TNF-α and IL-6 were significantly increased(P<0.05)in group M,P1,P2 and P3.Compared with group M,the gastric mucosal injury was alleviated in varying degrees,and the DI,PMN counts,AI and the expression of NF-κB in the gastric mucosa,and the serum levels of TNF-α and IL-6 were obviously decreased(P<0.05)in group P1,P2 and P3.Compared with group P3,the gastric mucosal injury was relieved,and the DI,PMN counts,AI and the expression of NF-κB in the gastric mucosa,and the serum levels of TNF-α and IL-6 were obviously decreased(P<0.05)in group P1.Conclusion Propofol can decrease NF-κB expression,inhibit inflammatory response and apoptosis,so as to reduce gastric mucosal injury after traumatic hemorrhagic shock and resuscitation in rabbits,and the effect of propofol is better before bleeding.