摘要目的 观察大潮气量机械通气大鼠血浆和支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)巨噬细胞炎症蛋白-1α(MIP-1α)含量以及肺组织MIP-1α mRNA和NF-κBp65 mRNA表达水平.方法 32只健康雄性Wistar大鼠随机(随机数字法)分为对照组,机械通气致肺损伤(VILI)组、地塞米松干预(DEX)组和布地奈德干预(BUD)组.给与相应处理后分别采用ELISA法检测各组大鼠BALF和血浆MIP-1α含量,采用RT-PCR法检测其肺组织MIP-1αmRNA和NF-κB p65mRNA表达水平,比较4组之间的差异,并将VILI,DEX,BUD组间MIP-1α mRNA与MIP-1α含量,MIP-1α mRNA与NF-κB p65 mRNA表达水平间进行直线相关分析.结果 DEX组和BUD组BALF及血浆中MIP-1α含量及肺组织MIP-1αmRNA和NF-κBp65 mRNA表达水平均明显低于VILI组(P＜0.05),同时肺组织损伤程度明显减轻;BUD组BALF和血浆中MIP-1α含量及肺组织MIP-1α mRNA和NF-κB p65 mRNA表达水平虽高于DEX组,但差异无统计学意义(P＞0.05).相关分析结果表明,肺组织MIP-1α mRNA表达量与BALF中MIP-1α含量呈正相关(r=0.895,P＜0.05);肺组织MIP-1α mRNA表达量与NF-κB p65 mRNA表达量呈正相关(r=0.801,P＜0.05).结论 糖皮质激素可能通过抑制NF-κB的活性而下调肺组织MIP-1α的表达,对VILI有一定防治作用;局部应用糖皮质激素对VILI的保护作用与全身用药的作用相似,且副作用小.

abstractsObjective To observe the content of macrophage inflammatory protein-1α(MIP-1α)in plasma and bronchoalveolar lavage fluid (BALF) and the expressions of MIP-1α mRNA and nuclear factor-kappa B( NFκB)p65 mRNA in the lung of rats subjected to mechanical ventilation with high tidal volume. Method Thirty-two healthy Wistar rats were randomly ( random number) divided into control group, ventilator induced lung injury (VILI) group,dexamethasone (DEX) group and budesonide (BUD) group. The content of MIP-1α in plasma and BALF were measured with ELJSA and the expressions of MIP-1α mRNA and NF-κBp65 mRNA in lung of rat were detected by RT-PCR. The data distributed were expressed as (-x) ± s and were compared among 4 groups. Furthermore, the correlation between the content of MIP-1α and the expression of MIP-1α mRNA, and the correlation between the expression of MIP-1α mRNA and the expression of NF-κBp65 mRNA were analyzed in the latter three groups. Results With lessened lung injury ,the content of MIP-1αin plasma and BALF and the expressions of MIP-1α mRNA and NF-κBp65 mRNA in lungs of rats of DEX and BUD groups were significantly lower than those in VILI group ( P ＜ 0.001 ). Although the content of MIP-1α in plasma and BALF and the expressions of MIP-1α mRNA and NF-κBp65 mRNA in lungs of rats of BUD group were higher than those of DEX group, but no significant differences were found between them ( P ＞ 0.05). Correlation study showed that positive correlations were xisted between the MIP-1α in plasma and the expression of MIP-1α mRNA in the lungs ( r = 0.895, P ＜ 0.05)and between the expression of MIP-1α mRNA and the expression of NF-κBp65 mRNA in the lungs ( r=0.801, P ＜ 0.05). Conclusions Glucocorticoid could down-regulate the expression of MIP-1α mRNA by inhibiting the activity of NF-κB in the lungs and may have preventive and therapeutic effect to VILI to some extent. The effect of glucocorticoid used locally against VILI is simnilar to that of systemic administration with lesser adverse reactions.