甲泼尼龙对犬低温体外循环后肺血管通透性的影响及机制

Effects and mechanisms of methylprednisolone on alveolar-capillary permeability after hypothermic cardiopulmonary bypass

目的研究中低温体外循环(CPB)对肺血管通透性的影响,观察术前注射甲泼尼龙5mg/kg是否能降低血管通透性,对CPB后的肺功能产生保护作用。方法健康家犬15只,随机分为3组:A组不进行CPB,作为非体外对照组;B组麻醉后注射10mL生理盐水,常规全麻和中度低温CPB,主动脉阻断90min,停CPB后继续维持至主动脉开放90min;C组麻醉后静脉给予甲泼尼龙5mg/kg,其余处理同B组。常规监测血流动力学和呼吸参数;B、C组分别在手术前、主动脉开放前、开放后30min和90min4个时间点采动脉血,ELISA法测定血浆基质金属蛋白酶-9(MMP-9)浓度,手术结束时,A、B、C3组均取完整左肺,进行机械通气和离体灌注,测量对液体的过滤系数。结果(1)主动脉开放30min和90min时,C组的肺血管阻力(PVR)较B组低(P<0.05),而氧合指数明显高于B组(P<0.05);(2)主动脉开放后B、C两组MMP-9的浓度均较术前明显升高(P<0.01),其中C组升高幅度明显小于B组,差异有统计学意义(P<0.01);(3)计算液体过滤系数,B组和C组明显高于A组(P<0.01),C组与B组相比Kf较小(P<0.05);(4)主动脉开放后的MMP-9最高值与Kf值呈正相关,与主动脉开放30min和90min时的氧合指数呈负相关。结论(1)低温CPB导致MMP-9大量释放,使肺血管通透性升高,导致肺损伤,肺的氧合功能下降;(2)术前注射甲泼尼龙能减少MMP-9的释放,降低肺血管通透性,对CPB后的肺损伤具有一定保护作用。

Purpose To investigate the effects and mechanisms of methylprednisolone （MP） on alveolar-capillary permeability after hypothermic cardiopulmonary bypass（CPB）. Methods Fifteen dogs were randomly divided into 3 groups. Group A was the control group without CPB; group B and group C were subjected to cardiopulmonary bypass and crossclamping the aorta for 90 minutes. After weaning from cardiopulmonary bypass, they were allowed to survive till 90 rain after aortic declamping. MP （group C） or saline （group B） was injected intravenously before surgery. Intraoperative and post- operative hemodynamic studies and lung parameters were recorded. Plasma levels of MMP-9 were measured at the following time points： before MP or saline was administered, aortic declamping, 30 min and 90 min after aortic declamping. Immediately after the animals were killed, the left lungs were obtained from 15 dogs and mounted in isolated perfused lung chambers for filtration coefficient （Kf） assessment. Results Compared with group B, there was a lower PVR and a higher oxygenation index （PaO2/FiO2） in group C after aortic declamping（P〈0.05）. After CPB there was a significant elevation in plasma levels of MMP-9, compared with those in group B, MP treatments were associated with lower plasma MMP-9. From isolated lung study, we found statistically significant changes in Kf between groups. In addition, statistically significant positive correlation was found between postbypass peak MMP-9 levels and lung Kf （P〈0.05）, and statistically significant negative correlation was found between MMP-9 and postbypass oxygenation indices. Conclusions （1） Hypothermic CPB could increase blood levels of MMP-9, and increase alveolar-capillary permeability. （2） MP of 5mg/kg could effectively reduce the release of MMP-9, and improve alveolar-capillary permeability.