【摘要】 为探讨内毒素休克时肺动脉高压的发生机制,实验观察了N-乙酰半胱氨酸(N-acetylcysteine,NAC)、NO及CO 在脂多糖(lipopolysaccharide,LPS)诱导的肺动脉反应性变化中的作用。用雄性家兔24只,制备约3mm宽的肺动脉环。实验结果显示:LPS孵育7h后,肺动脉对1μmol／L乙酰胆碱介导的内皮依赖性舒张反应降低,但对非内皮依赖性舒张剂硝普钠的反应性无明显改变。自由基清除剂(NAC)、L-精氨酸(NO供体)和氯化血红素(CO供体)可分别减轻LPS的上述作用。而应用血红素氧合酶-1(heme oxygenase-1,HO-1)阻断剂锌原卟啉抑制CO产生后则增强LPS的上述作用。N-硝基-L- 精氨酸甲酯(L-NAME,一氧化氮合酶抑制剂)抑制NO的产生后使各组肺动脉对乙酰胆碱的反应由舒张变为收缩,对1μmol／L 苯肾上腺素的收缩反应显著增强,说明NO和CO在肺动脉反应性改变中发挥重要作用。上述结果提示:抗氧化或给予 NO、CO可显著改善LPS引起的内皮依赖性舒张反应减弱。因此,多种因素参与了本实验中内毒素引起的肺动脉高压的发生。更多还原

【Abstract】 To explore the underlying mechanism(s) of pulmonary arterial hypertension in endotoxic shock, the roles of N-acetylcysteine (NAC), nitric oxide (NO) and carbon monoxide (CO) were investigated. Pulmonary arterial rings (3-mm width) were prepared from 24 rabbits. Lipopolysaccharide (LPS), after 7- hour incubation, decreased the endothelium-dependent relaxation response of the arterial ring (pre-contracted with phenylephrine) to acetylcholine (1 μmol/L), but did not affect the endothelium-independent relaxation response to sodium nitroprusside. The LPS effects were reduced by a concomitant incubation with the free radical scavenger (NAC), NO donor (L-arginine), and CO donor (hemin), respectively. On the other hand, the LPS effects were enhanced by applying heme oxygenase-1 (HO-1) inhibitor (zinc protoporphyrin) to block CO production. The response to acetylcholine changed from relaxation to contraction, however, the contractile response to phenylephrine increased significantly after pre-incubation with nitric oxide synthase (NOS) inhibitor (L-NAME) to block NO production, confirming the importance of CO and NO. These results show that LPS impairs endothelium-dependent relaxation of the pulmonary artery, which can be greatly reduced by the antioxidant, or by supplying with NO and CO. Thus, multiple factors are involved in this model of endotoxin-induced pulmonary hypertension.更多还原