谷氨酰胺对脂多糖致急性肺损伤大鼠肺组织核因子-κB的影响

Effects of glutamine on changes of nuclear factor-Kappa B in acute lipopolysaccharide lung injury： experiment with rats

目的探讨谷氨酰胺对脂多糖致急性肺损伤大鼠肺组织核因子（NF）-κB和肺组织病理学变化的影响。方法静脉注射脂多糖（LPS）5mg／kg复制大鼠急性肺损伤模型。雄性SD大鼠50只，随机分为5组（n=10）：对照组（A组）；LPS组（B组）；C、D、E组为谷氨酰胺＋LPS组，分别于LPS注入前1h、LPS注入同时、LPS注入后1h，静脉注射谷氨酰胺0．75g／kg。于注射LPS后4h处死动物，测定肺组织NF-κB mRNA表达、肿瘤坏死因子-α（TNF-α）含量、超氧化物歧化酶（SOD）活性以及丙二醛（MDA）含量，HE染色光镜观察肺组织病理变化。结果与B组比较，C、D组不同程度逆转肺组织SOD活性的下降，抑制肺组织NF-κB mRNA、TNF-α及MDA水平的升高（P〈0．01），光镜下可见肺组织损伤明显减轻。E组上述指标改善不明显。结论谷氨酰胺早期给药对脂多糖性急性肺损伤起保护效应，其机制与抑制肺组织NF-κB mRNA的过度表达，从而抑制肺部炎症反应有关。

Objective To investigate the effects of glutamine on the changes of nuclear factor （NF）-κB and lung pathology in acute lung injury. Methods Forty SD rats underwent injection of lipopolysaccharide （LPS） 5 mg/kg into the femoral vein, and were randomly divided into 4 equal groups： Group B. undergoing injection of glutamine 0. 75 g/kg into the femoral vein lh before LPS injection, Group C undergoing injection of glutamine and LPS simultaneously, and Group D undergoing injection of glutamine 1h after LPS injection, and Group E without glutamine injection. Another 10 rats underwent injection of normal saline to be used as controls （ Group A）. Four hours after the LPS injection the rats were killed with their lungs taken out. RT-PCR was used to detect the level of nuclear factor （NF）-κB mRNA expression. ELISA was used to detect the tumor necrosis factor （TNF） - in lung. The activity of superoxide dismutase （SOD） was examined by hydroxylamine method, and the malondialdehyde level was determined by thiobarbituric acid （TBA） method. Results The lung NF-κB mRNA expression levels and TNF- levels of Groups B, C, D, and E were all significantly higher than that of Group A （ all P 〈 0. 01 ）. The lung NF-κB mRNA expression levels and TNF- levels of Groups C and D were all significantly lower than those of Group B （ P 〈 0. 01 ）. However, there were no significant differences in lung NF-κB mRNA expression level and TNF- level between Group B and Group E （ both P 〉 0. 05 ）. The SOD activity of Group B was significantly lower than that of Group A and the MDA content of Group B was significantly higher than that of Group A （ both P 〈 0. 05 ）. The SOD activity levels of Groups C and D were significantly higher than that of Group B and the MDA content of Groups C and D were significantly lower than that of Group B （ P 〈 0. 01 or P 〈 0. 05 ）. However there were no significant differences in lung SDD activity and MDA content between Groups B and E （ both P 〉 0. 05 ）. Obvious inflammatory changes were seen in the lungs of Groups B and E at the similar extent. Only slight infiltration could be seen in Groups C and D. The lung of Group A was normal. Conclusion Early glutamine administration protects the lung against acute LPS injury. The mechanism may be inhibition of the overexpression of NF-κB mRNA.