甲泼尼龙对低温体外循环后肺血管内皮功能的影响

Effects of Methylprednisolone on Pulmonary Endothelial Function after Hypothermic Cardiopulmonary Bypass

目的研究甲泼尼龙5mg/kg是否能有效抑制体外循环(CPB)诱发的炎症反应,并对肺血管内皮功能产生保护效应。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:麻醉后注射生理盐水10mL,常规全麻和CPB,主动脉阻断90min;C组:麻醉后静脉给予甲泼尼龙5mg/kg,其余处理同B组。B、C组分别在手术前及主动脉开放前、开放后30min和90min4个时间点采动脉血,放免法测定血浆白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-8(IL-8)和白介素-10(IL-10)水平;手术结束时,A、B、C3组均取右肺动脉段,固定于张力传感器,测定血管环内皮依赖性和非内皮依赖性扩张能力的变化。结果CPB前各细胞因子水平无统计学差异,CPB使IL-1β、TNF-α、IL-6、IL-8和IL-10产生增多,血浆水平明显升高(P<0.01);C组IL-1β、TNF-α、IL-6和IL-8升高幅度较小,与B组相比有明显差异,而IL-10水平明显高于B组。3组肺血管环对去甲肾上腺素的反应相似,ACh产生的最大舒张反应在CPB后的肺动脉环明显降低,只有A组的50%(P<0.001);体外前注射甲泼尼龙5mg/kg使ACh产生的最大舒张反应从31%升高到48%(P<0.01);各组动脉环对硝酸甘油产生的舒张反应相似,其Rmax和EC50在3组间无统计学差异。结论术前注射甲泼尼龙5mg/kg能有效抑制CPB诱发的炎症反应、保护血管内皮功能,改善肺动脉的内皮依赖性舒张功能。

Purpose To investigate if methylprednisolone(MP) could attenuate inflammatory responses to cardiopulmonary bypass(CPB) and improve pulmonary endothelial function. Methods Fifteen dogs were randomly divided into 3 groups.Group A acted as the control group without CPB;group B and group C were subjected to cardiopulmonary bypass and crossclamping the aorta for 90 min.MP (group C) or saline (group B) was injected intravenously before surgery.Plasma levels of IL-1β?TNF-α?IL-6?IL-8 and IL-10 were measured at the following time points:before MP or saline were administered,aortic declamping,30 min and 90 min,after aortic declamping.Immediately after the animals was killed,pulmonary arterial rings were obtained and mounted in organ chamber for assessment of endothelial function with endothelium-dependent (acetylcholine) or non-endothelium-dependent (nitroglycerin) studies. Results After CPB there was a significant elevation in plasma levels of IL-1β?TNF-α?IL-6?IL-8 and IL-10.Compared with those in group B,MP treatments were associated with lower plasma IL-1β?TNF-α?IL-6?IL-8 and increased IL-10.Similar maximal contractions to norepinephrine were observed in 3 groups of vascular rings.Maximal relaxation response to acetylcholine was reduced after bypass to 50% of control values (P<0.001).Treatments with MP significantly improved the relaxation from 31% to 48% (P<0.01).Maximal relaxation response to nitroglycerin was similar in three groups. Conclusions MP (5 mg/kg) could effectively attenuate inflammatory responses to CPB and improved pulmonary endothelial function.