【摘要】 为探讨八肽胆囊收缩素 (CCK 8)缓解内毒素休克时肺动脉高压的作用机制 ,应用离体血管环张力测定技术及扫描电镜方法 ,观察了CCK 8对肿瘤坏死因子α (TNF α)引起的肺动脉反应性及肺动脉内皮细胞超微结构变化的影响。结果显示 :离体肺动脉经TNF α (4 0 0 0U/ml)孵育 2h对苯肾上腺素 (PE)的收缩反应、对乙酰胆碱(ACh)及硝普钠 (SNP)的内皮依赖性及非内皮依赖性舒张反应均无明显影响。TNF α (4 0 0 0U/ml,孵育 7h或 14h)可降低离体肺动脉对ACh介导的内皮依赖性舒张反应 ;CCK 8(0 5 μg/ml)逆转了TNF α的上述作用。CCK 8(0 5μg/ml)本身对正常肺动脉舒缩反应无明显影响。扫描电镜显示 ,CCK 8(0 5 μg/ml)对TNF α (4 0 0 0U/ml,7h)损伤的肺动脉内皮细胞有保护作用。结果提示 ,CCK 8可逆转TNF α对内皮依赖性舒张反应的抑制作用 ,减轻内皮细胞结构损伤 ,这可能是CCK 8抗内毒素休克时肺动脉高压并具有细胞保护作用的机制之一。更多还原

【Abstract】 To explore the mechanism underlying cholecystokinin octapeptide (CCK 8) induced attenuation of pulmonary arterial hypertension (PAH) in endotoxic shock, the effects of CCK 8 on the changes in rabbit pulmonary arterial reactivity induced by tumor necrosis factor alpha (TNF α) were observed with the isolated arterial ring technique, and the ultrastructure of pulmonary arterial endothelium was observed under a scanning electron microscope. The contractile response to α adrenoceptor agonist phenylephrine (PE), the endothelium dependent relaxation response to acetylcholine (ACh) and the endothelium independent relaxation response to sodium nitroprusside (SNP) were not affected by TNF α (4?000 U/ml) after incubation for 2 h, while, if the incubation time was prolonged to 7 or 14 h, the relaxation response of pulmonary artery to ACh was depressed significantly, which, however, could be reversed by concomitant exposure to CCK 8 (0 5 μg/ml). Incubation of pulmonary artery with CCK 8 (0 5 μg/ml) alone did not bring out any contractile responses. Moreover, CCK 8 (0 5 μg/ml) alleviated the ultrastructural lesions induced by TNF α (4?000 U/ml). These results suggest that CCK could protect pulmonary arterial endothelium against the detrimental effects by TNF α.[WT5HZ]更多还原