高碳酸血症对大鼠机械通气肺损伤时炎症因子和p38MAPK表达的影响

Effects of Hypercapnia on Expression of Inflammatory Cytokines and p38MAPK in Ventilator-Induced Lung Injury in Rats

目的:探讨高碳酸血症对大鼠机械通气性肺损伤(VILI)时炎症因子和p38MAPK表达的影响。方法:健康雄性Wistar大鼠30只,体重220～280g,采用随机数字表法,将大鼠随机分3组(n=10):对照组(C组)、机械通气肺损伤组(V组)和高碳酸血症组(H组)。C组保留自主呼吸,V组和H组行机械通气4 h。采用高气道压机械通气模式制备机械通气性肺损伤模型。H组通过调整吸入的CO2浓度来维持动脉血PaCO2分别为80～100mmHg。机械通气结束时,测定支气管肺泡灌洗液(BALF)中总蛋白、TNF-α和巨噬细胞炎症蛋白-2(MIP-2)的浓度;取肺组织,测定湿干重比(W/D比)、细胞间粘附分子(ICAM-1)和p38MAPK蛋白的表达水平以及p38MAPK的活性,并观察病理学结果,进行肺损伤评分。结果:与C组比较,V组肺损伤评分、W/D比、ICAM-1表达水平、BALF中总蛋白浓度、TNF-α和MIP-2浓度和肺组织p38MAPK活性升高,PaO2降低(P<0.05);与V组比较,H组肺损伤评分、W/D比、ICAM-1表达水平、BALF中总蛋白浓度、TNF-α和MIP-2浓度和肺组织p38MAPK活性降低,PaO2升高(P<0.05)。结论:高碳酸血症通过调节p38MAPK的表达,从而抑制炎症反应减轻大鼠机械通气肺损伤。

Objective： To investigate the effects of hypercapnia on the inflammatory cytokines and p38MAPK in ventilator lung injury in rats.Methods： Thirty male Wistar rats weighting 250～280g were randomly divided into 3 groups（n=10 each）：control group（group C）,VILI group（group V）,hypercapnia group（group H）.A rat model of lung injury induced by ventilation with high peak inspiratory pressure（PIP）.Parameter of ventilation： PIP=25cmH2O,PEEP=2cmH2O,the fraction of inspiratory O2 50% and adjusting the level of CO2 to maintained PaCO2 of group V and group H at 35～45mmHg and 80～100mmHg respectively.The rats were sacrificed by exsanguination 4h of mechanical ventilation and the lung tissues were removed for microscopic examination,lung wet to dry weight ratio（W/D）,determination of ICMA-1（by immuno-histochemistry）,p38 and phosphorylated p38（p-p38） expresstion（by Western blotting） and determination of TNF-A,MIP-2（by enzyme linked immunosorbent assay） and total of protein concentration in bronchoalveolar lavage fluid（BALF）.Results： Compared with group C,the lung injury score,W/D ratio,TNF-A,MIP-2,total protein concentrations in BALF,ICAM-1 expression and p38MAPK activity in lung tissue were increased,PaO2 were decreased in groups V（P〈0.05）.Compared with group V,the lung injury score,W/D ratio,TNF-A,MIP-2,total protein concentrations in BALF,and MAD content,ICAM-1 expression and p38MAPK activity in lung tissue were decreased,PaO2 and were increased in group P（P〈0.05）.Conclusions： Hypercapnia attenuated ventilator-induce lung injury by regulating the expression of p-p38MAPK that inhibit the expression of inflammatory cytokines in rat lung tissues.