EFFECT OF ENDOTOXIN‐ENHANCED HEPATIC REPERFUSION INJURY ON ENDOTHELIUM‐DEPENDENT RELAXATION IN RAT AORTA
EFFECT OF ENDOTOXIN‐ENHANCED HEPATIC REPERFUSION INJURY ON ENDOTHELIUM‐DEPENDENT RELAXATION IN RAT AORTA
复制标题
内毒素增强肝再灌注损伤对大鼠主动脉内皮依赖性舒张的影响
作者：
Rosemary McKenna;R. Laskey;Ying Wang;H. Jaeschke;W. Mathews
摘要我们研究了多器官衰竭两次打击模型中的内皮功能。雄性Fischer大鼠进行20分钟的部分肝缺血，然后再灌注，并在再灌注30分钟时给予0.5 mg/kg沙门氏菌内毒素。再灌注4或24小时后，制备主动脉环，并将其悬浮在生物测定浴中，用苯丙氨酸收缩，并检查对乙酰胆碱的内皮依赖性舒张和使用硝酸甘油的内皮非依赖性舒张。在暴露于内毒素增强的再灌注损伤的动物的环中，在4小时和24小时，对乙酰胆碱的内皮依赖性舒张受损。在再灌注24小时，乙酰胆碱舒张的EC 50从45 ± 8 nM显著增加至258 ±105 nM。内皮非依赖性舒张硝酸甘油不受影响。21-氨基类固醇甲磺酸替拉扎德（U-74006 F）可预防内皮功能障碍;在再灌注24小时时，U-74006 F治疗动物中乙酰胆碱松弛的EC 50为55 ± 8 nM。因此，在该多器官衰竭模型中，内皮功能受损，甲磺酸替拉扎德可预防该损伤。
ABSTRACT We have investigated endothelial function in a two-hit model of multiple organ failure. Male Fischer rats were subjected to 20 min of partial hepatic ischemia followed by reperfusion and administration of .5 mg/kg Salmonella enteritidis endotoxin at 30 min of reperfusion. After either 4 or 24 h of reperfusion, rings of aorta were prepared and suspended in bioassay baths, contracted with phenylephrine, and examined for endothelium-dependent relaxation in response to acetylcholine and endothelium-independent relaxation using nitroglycerin. Endothelium-dependent relaxation to acetylcholine was impaired in rings from animals exposed to endotoxin-enhanced reperfusion injury at both 4 h and 24 h. At 24 h of reperfusion the EC50 for acetylcholine relaxation was significantly increased from 45 ± 8 nM to 258 ±105 nM. Endothelium-independent relaxation to nitroglycerin was not affected. The 21-aminosteroid Tirilazad mesylate (U-74006F) prevented endothelial dysfunction; at 24 h of reperfusion the EC50 for acetylcholine relaxation in U-74006F-treated animals was 55 ± 8 nM. Thus, endothelial function is impaired in this model of multiple organ failure and this impairment is prevented by Tirilazad mesylate.