内毒素诱导兔肺动脉平滑肌iNOS生成中NF-κB作用的探讨

EFFECT OF NF κB ON iNOS SYNTHESIS IN RABBIT PULMONARY SMOOTH MUSCLE INDUCED BY ENDOTOXIN

目的和方法：实验采用内毒素的主要成分脂多糖（ＬＰＳ）离体孵育去内皮兔肺动脉环方法，观察血管收缩性的改变，并加入诱生型ＮＯ生成抑制剂氨基胍（ＡＧ）以及核转录因子（ＮＦκＢ）的拮抗剂吡咯烷二硫代氨基甲酸盐（ＰＤＴＣ）后观察了血管收缩性的变化。结果：ＬＰＳ孵育１６ｈ后血管环对新福林（ＰＥ）的反应性明显减低（Ｐ＜０．０１），与ＬＰＳ孵育组比较，ＬＰＳ与ＡＧ共同孵育后血管环反应性增加，ＰＤＴＣ预孵育血管环后再用ＬＰＳ孵育，血管环反应性也较ＬＰＳ孵育的血管环反应明显增加。经ＬＰＳ孵育的血管环用ＮＯ生成抑制剂Ｌ硝基精氨酸（ＬＮＮＡ）处理后，对血管收缩剂ＰＥ的反应性有明显增加，而ＰＤＴＣ预孵育组的血管环用ＬＮＮＡ处理后收缩反应性无明显增加。结论：ＬＰＳ离体孵育去内皮肺动脉后，血管平滑肌ｉＮＯＳ诱生，致使血管反应性降低，而ＮＦκＢ在肺动脉平滑肌ｉＮＯＳ诱生中起信息传递作用。

Aim and Methods: To study whether the defects in contractility could be induced in endothelium denuded pulmonary artery ring by exposure to lipopolysaccharides, (LPS) in vitro, and whether contractile response was altered after the action of aminoguanidine (AG) an inhibitor of inducible nitric oxide (NO) synthesis as well as pyrrolidine dithiocarbamate (PDTC), an antagonist of NF κB. Results: The contractions of vessels to phenylephrine (PE) were suppressed ( P <0.01) by incubation with LPS for 16h in comparison with control. The addition of AG during the incubation improved tissue reactivity to PE. The sensitivity of vessels to PE improved markedly after pre incubated with PDTC for 1.5 h before the incubation with LPS. After treatment with N ω nitro l arginine (L NNA) an inhibitor of NO synthesis, the reactivity of rings to PE improved significantly in LPS incubated group, while the change was not significant in PDTC pre incubated group. Conclusion: iNOS was induced in vascular smooth muscle after exposure to LPS, while NF κB acted as a signal transduct substance in the induction of iNOS in pulmonary smooth muscle.