异丙酚联合地塞米松对早期脓毒症大鼠急性肺损伤的保护作用及机制

Protective effect and mechanism of propofol and dexamethasone on acute lung injury in septic rats during the early phase

目的探讨异丙酚联合地塞米松对早期脓毒症大鼠急性肺损伤的保护作用及可能机制。方法将25只雄性SD大鼠随机分为5组各5只,N组尾静脉注射0.9%氯化钠注射液10 mL;另四组注射脂多糖(LPS)10 mg/kg,制作脓毒症急性肺损伤模型。制模后L组不用药,D组注射地塞米松0.1 mg/kg;P组注射异丙酚5 mg/kg,继以异丙酚5 mg/(kg.h)的速度持续缓慢静脉泵注4 h;PD组注射地塞米松0.1 mg/kg和异丙酚5 mg/kg,继以异丙酚5 mg/(kg.h)的速度静脉泵注至4 h。各组均于造模后4 h麻醉处死,行动脉血气分析,测定肺组织湿/干重量比值(W/D),RT-PCR法检测肺组织水通道蛋白1(AQP1)mRNA表达水平。结果与L组比较,D、P、PD组肺组织W/D值明显降低,AQP1 mRNA表达水平明显升高,动脉血气指标明显改善;PD组各指标较D、P组改善更明显。结论异丙酚及地塞米松对早期脓毒症大鼠急性肺损伤有协同保护作用,其机制可能为上调肺毛细血管内皮AQP1 mRNA表达水平,提高肺间质内水肿液的跨内皮转运速率。

Objective To observe the protective effect of propofol and dexamethasone on acute lung injury in septic rats during the early phase. Methods Twenty-five male SD rats were randomly divided into 5 groups with 5 in each, the group N was given 0.9% sodium chloride injection via tail vein of 10 mL; the other four groups were given LPS of 10 mg/ kg, the acute lung injury model induced by sepsis were made. Then the group L was not given drugs, group D was given dexamethasone of 0.1 mg/kg; group P was given propofol of 5 mg/kg, and then 5 mg/（ kg · h）propofol was given by Syringe pumps for 4 h; group PD was given dexamethasone of 0.1 mg/kg and propofo[ of 5 mg/kg, then 5 rag/（ kg ·h）propo- fol was given by Syringe pumps for 4 h. The rats in the anesthesia were killed in 4 h. Arterial blood gas analysis, lung tissue wet/dry weight ratio （W/D） were done, and AQP1 mRNA expression levels in lung tissue were detected by RT-PCR in each group. Results Compared with the group L, the lung tissue W/D were significantly lower, while the expression of AQP1 mRNA were increased significantly, as well as the arterial blood gas were improved in group D, P, PD; these changes were more evident in the group PD, compared with the group D and P. Conclusion The propofol and dexamethasone have cooperative protective effects on acute lung injury at the early stage of sepsis, the mechanism maybe associated with increasing the level of expression of lung AQPI mRNA, and improving the transendothelial migration rate of edema fluid in interstitial lung tissue.