CAJ | 학술논문

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3 mm宽的肺动脉环.实验结果显示:LPS孵育7 h后,肺动脉对1 μmol/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1 μmol/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.周此,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.
위탐토내독소휴극시폐동맥고압적발생궤제,실험관찰료N-을선반광안산(N-acetylcysteine,NAC)、NO급CO재지다당(lipopolysaccharide,LPS)유도적폐동맥반응성변화중적작용.용웅성가토24지,제비약3 mm관적폐동맥배.실험결과현시:LPS부육7 h후,폐동맥대1 μmol/L을선담감개도적내피의뢰성서장반응강저,단대비내피의뢰성서장제초보납적반응성무명현개변.자유기청제제(NAC)、L-정안산(NO공체)화록화혈홍소(CO공체)가분별감경LPS적상술작용.이응용혈홍소양합매-1(heme oxygenase-1,HO-1)조단제자원계람억제CO산생후칙증강LPS적상술작용.N-초기-L-정안산갑지(L-NAME,일양화담합매억제제)억제NO적산생후사각조폐동맥대을선담감적반응유서장변위수축,대1 μmol/L분신상선소적수축반응현저증강,설명NO화CO재폐동맥반응성개변중발휘중요작용.상술결과제시:항양화혹급여NO、CO가현저개선LPS인기적내피의뢰성서장반응감약.주차,다충인소삼여료본실험중내독소인기적폐동맥고압적발생.
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 24rabbits. 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, confirning 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.