允许性高碳酸血症对大鼠机械通气相关性肺损伤NF-κB表达的影响

Effects of Hypercapnia on Expression of NF-κB in Ventilator-Induced Lung Injury in Rats

目的：探讨允许性高碳酸血症对大鼠机械通气相关性肺损伤（VILI）时NF-κB表达的影响。方法：健康雄性Wistar大鼠30只,体重220~280 g,采用随机数字表法,将大鼠随机分3组（n=10）：对照组（C组）保留自主呼吸、机械通气肺损伤组（V组）和VILI＋高碳酸血症干预治疗组（H组）行机械通气4 h。采用吸气相高气道压机械通气模式制备机械通气相关性肺损伤模型。H组通过调整吸入的CO2浓度来维持动脉血PaCO_2分别为80~100 mm Hg。于机械通气15 min时、机械通气1 h、2 h和4 h时记录MAP,采集股动脉血样,进行动脉血气分析,记录PaO_2;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NF-κb蛋白的表达水平,并观察病理学结果,进行肺损伤评分。测定肺组织丙二醛（MDA）含量及过氧化物歧化酶（SOD）活性。结果：与C组比较,V组和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、MDA含量和肺组织NF-κB活性升高,PaO_2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NF-κB表达降低,SOD活性增强,PaO_2升高（P〈0.05）。结论：允许性高碳酸血症可下调NF-κB的表达,从而抑制炎症反应减轻大鼠机械通气相关性肺损伤。

Objective： To investigate the effects ofhypercapnia on expression of NF-κB in ventilator lung injury in rats. Methods： thirty male Wistar rats weighting 250~280 g were randomly divided into 3 groups （n=10 each）： control group （C group）, VILI group（V group）,VILI＋ hypercapnia group （H group）. A rat model of lung injury induced by ventilation with high peak inspiratory pressure（PIP）. Parameter of ventilation： PIP=25 cm HzO, PEEP=2 cm H20, the fraction of inspiratory 02 50% and adjusting the level of COs to main- tained PaCe2 of group V and group H at 35 ~45 mmHg and 80~ 100 mmHg respectively. The rats were sacrificed by exsanguination at 4 h of mechanical ventilation and the lung tissues were removed for microscopic examination, lung wet to dry weight ratio （W/D）, deter- mination of ICMA-1 （by immune histochemistry）, NF-KB expression （by Western blotting） and determination of TNF-α, MIP-2 （by en- zyme linked immunosorbent assay）, MDA and total of protein concentration in bronch-alveolar lavage fluid（BALF）. Results： Mechanical ventilation with high PIP in group V induced serious histopathologic damage, significant increase in TNF-α, MIP-2 and total protein con- centration in BALF, ICAM-1 and NF-κB, MDA in lung tissue and W/D ratios as compared with group C （P〈0.05）. The indexes above were significant decreased in group H compared with group V （P〈0.05）. Conclusions： Hypercapnia attenuated ventilator-induce lung in- jury by down regulating the expression of NF-κB that inhibit the expression of inflammatory cytokines in rat lung tissues.