高碳酸血症对急性肺损伤时核因子-κB和TNF-α的影响  

EFFECTS OF HYPERCAPNIA ON NUCLEAR FACTOR-KAPPA B AND TNF-α IN ACUTE LUNG INJURY MODELS

作　　者：杨丽丽[1] 戢新平[1] 刘志[1] 刘刚[2] 关福兰[3] 

机构地区：[1]中国医科大学第一临床学院急诊科 [2]中国医科大学呼吸疾病研究所 [3]中国医科大学药理学教研室,辽宁沈阳110001

出　　处：《中国应用生理学杂志》2004年第4期396-400,共5页Chinese Journal of Applied Physiology

基　　金：辽宁省教育厅高等学校科学研究项目(202013152)

摘　　要：目的观察高碳酸血症对兔急性肺损伤(ALI)模型核因子κB(NFκB)和TNFα表达的影响,探讨其对ALI的作用机制。方法22只新西兰大白兔随机分为对照组(C组)、非高CO2通气组(N组)、高CO2(8%)通气组(H组)。N组和H组通过静脉注射油酸(0.1ml/kg)复制ALI模型,观察肺组织中NFκB的表达情况、血清和BALF中TNFα的含量变化及肺组织病理学改变。结果血清及BALF中TNFα含量N组和H组高于C组(P<0.01,P<0.05),且N组高于H组(P<0.05)。免疫组化及蛋白印迹分析表明H组NFκB的表达较N组减少(P<0.05)。H组气道峰压显著低于N组,动态胸肺顺应性显著高于N组。动脉血氧分压H组明显高于N组(均P<0.05)。H组病理组织学改变较N组明显减轻。结论机械通气时吸入8%的CO2所致高碳酸血症对ALI动物模型有保护作用,其机制可能与高碳酸血症抑制NFκB的活化,从而抑制炎症介质如TNFα的表达有关。Aim: To observe the effects of hypercapnia on nuclear factor kappaB and TNF α in acute lung injury models. Methods: Six of the twenty two healthy New Zealand white rabbits were randomly allocated to control group(Group C), the other sixteen rabbits were injected with oleic acid (0.1 ml/kg) intravenously, then were randomized to normocapnic group(Group N, n =8) versus hypercapnic group(Group H, n =8). TNF α of serum and bronchoalveolar lavage fluid(BALF) and the expression of nuclear factor kappaB in the lung were analyzed after three hours’ mechanical ventilation. Results: TNF α of serum and bronchoalveolar lavage fluid in Group N and H was significantly higher than that in Group C ( P <0.01), and that of Group N was higher than that of Group H( P <0.05). The expression of nuclear factor kappaB in Group H was less than that in Group N by both immunohistochemistry and Western blot analysis. Peak airway pressure in Group H was significantly lower than that in Group N and the dynamic lung compliance was significantly higher than that in Group N( P <0.05). PaO 2 in Group H was significantly higher than that in Group N( P< 0.05). Histologic damage in Group N was significantly severer than that in Group H.Conclusion: Hypercapnia is protective in this in vivo model of ALI. The mechanisms might be associated with the prohibition of nuclear factor kappaB and then the decreased expression of TNF α by hypercapnia.

关 键 词：高碳酸血 急性肺损伤 机械通气 核因子-ΚB TNF-Α 

分 类 号：R3[医药卫生—基础医学]