肺缺血预处理在深低温停循环中肺保护的实验

The Experimental Research of Protective Mechanism of Lung Ischemic Preconditioning in Deep Hypothermic Circulatory Arrest Extracorporeal Circulation

目的评估肺缺血预处理(ischemic preconditioning,IP)在深低温停循环(deep hypothermic circulatory arrest,DHCA)心外科手术中对肺功能的保护作用。方法幼猪在体DHCA实验模型,分常温再灌注组(基线组)、无肺IP的DHCA组(对照组)和有肺IP的DHCA组(IP组),测体外循环(extracorporeal circulation,ECC)前、结束即刻和结束后1h肺静态顺应性和肺血管阻力值;以左房血和肺动脉血中相关炎性介质浓度和白细胞黏附分子受体表达值的比值(LA/PA),反应肺区释放量和激活量;ECC结束即刻取肺组织行光、电镜观察。结果三组ECC后,肺静态顺应性均显著降低,肺血管阻力均显著增加,IP组较对照组有显著差异,显示了明显的肺保护作用。三组ECC后,肿瘤坏死因子(TNF)-α、白介素(IL)-10的LA/PA比值均显著增加,而IL-8比值仅在对照组和IP组明显增加;TNF-α比值IP组较其他两组无显著差异;IL-8、IL-10比值,IP组较对照组均显著降低;中性粒细胞CD18表达比值,仅在对照组ECC后1h相对于ECC前显著降低;单核细胞CD18表达比值,对照组较基线组显著降低。光镜和电镜下的肺损伤程度IP组较对照组明显减轻。结论本研究示DHCA加剧ECC肺区炎性反应,证实了肺IP可以减轻DHCA情况下缺血再灌注引起的炎性反应性肺损伤,从而保护肺功能。

OBJECTIVE To evaluate the protective effect of using lung ischemic preconditioning（IP） prior to cardiac surgery with deep hypothermic circulatory arrest（DHCA） extracorporeal circulation（ECC）.METHODS Using an animal model of DHCA ECC,piglets were divided randomly into three groups：normothermic ECC reperfusion group（baseline group）,DHCA group without lung IP（control group） and DHCA group with lung IP（IP group）.Lung static compliance and pulmonary vascular resistance were measured at the beginning and end of ECC and one hour later.Blood was simultaneously drawn from the left atrium（LA） and the pulmonary artery（PA）,the level of TNF-α、IL-8 and IL-10 were determined,as well as the adhesion molecules CD18 on leukocytes.As a measure of the pulmonary release,ratios of LA/PA levels were calculated.A piece of lung tissue was taken at the end of ECC to evaluate morphology by light and electron microscopy.RESULTS After ECC lung static compliance was significantly decreased whereas pulmonary vascular resistance was significantly increased,IP group showed the significant protective effect.After ECC LA/PA ratios for TNF-α,IL-10 were significantly increased in each groups,whereas the ratios for IL-8 were significantly increased only in control and IP groups,LA/PA ratios for TNF-α had no significant difference between IP group and the other two groups;LA/PA ratios for IL-8 in IP group were significantly decreased compared with control group,LA/PA ratios for IL-10 both in control group and IP group were significantly increased compared with baseline group,LA/PA ratios for IL-10 in IP group were significantly decreased compared with control group.LA/PA ratios of CD18 on neutrophils only in control group at 1h post-ECC were significantly decreased compared with pre-ECC,LA/PA ratios of CD18 on monocytes in control group were significantly decreased compared with baseline group.Histologic findings showed less lung injury in IP groups than in control groups.CONCLUSION Our study indicats that DHCA aggravated lung inflammatory response during ECC,lung IP had a protective effect in lung ischemia reperfusion injury during DHCA.