Interaction of platelet activating factor, reactive oxygen species generated by xanthine oxidase, and leukocytes in the generation of hepatic injury after shock/resuscitation.
Interaction of platelet activating factor, reactive oxygen species generated by xanthine oxidase, and leukocytes in the generation of hepatic injury after shock/resuscitation.
复制标题
血小板活化因子、黄嘌呤氧化酶产生的活性氧和白细胞在休克/复苏后肝损伤产生中的相互作用。
DOI：
10.1097/00000658-200003000-00012
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发表时间：
2000
影响因子：
9
通讯作者：
Bulkley,GB
中科院分区：
文献类型：
--
作者：
Yamakawa,Y;Takano,M;Patel,M;Tien,N;Takada,T;Bulkley,GB
目的探讨血小板活化因子（PAF）、黄嘌呤氧化酶（xanthine oxidase，xanthine oxidase）、活性氧化剂和白细胞在休克/复苏（shock/resurrection，S/R）后肝损伤发病机制中的作用。然而，精确的线性序列的机制，随后的肝损伤后S/R仍有待characterized.MethodsUnheparinized雄性大鼠流血的的平均血压为45±3毫米汞柱。休克2小时后，他们被复苏，通过再输注脱落的血液（抗凝与柠檬酸盐-磷酸盐-葡萄糖）和晶体，并观察了未来的6或24 hours.ResultsS/R引起的氧化肝谷胱甘肽和产生centrolobular白细胞积累在6小时，其次是centrolobular肝细胞损伤在24小时。这些成分中的每一种都通过使用WEB 2170抑制PAF、使用别嘌呤醇抑制黄嘌呤氧化酶、使用N-乙酰半胱氨酸进行抗氧化处理或使用长春碱诱导的重度白细胞减少症而减弱。在每种情况下，6小时时白细胞蓄积的程度与24小时时观察到的肝细胞损伤相关。然而，黄嘌呤氧化酶抑制与别嘌呤醇未能进一步衰减的小水平的残留肝细胞损伤leukopenic rats.ConclusionThese研究结果表明，黄嘌呤氧化酶在再灌注时产生的反应性氧化剂，刺激PAF，介导肝细胞损伤触发白细胞积累，主要是在小叶中央窦。
ObjectiveTo evaluate the putative relation of platelet activating factor (PAF), xanthine oxidase, reactive oxidants, and leukocytes in the pathogenesis of hepatic injury after shock/resuscitation (S/R) in vivo.BackgroundReactive oxygen metabolites generated by xanthine oxidase at reperfusion have been found to trigger postischemic injury in many organs, including the liver. However, the precise linear sequence of the mechanism of consequent hepatic injury after S/R remains to be characterized.MethodsUnheparinized male rats were bled to a mean blood pressure of 45±3 mmHg. After 2 hours of shock, they were resuscitated by reinfusion of shed blood (anticoagulated with citrate-phosphate-dextrose) and crystalloid and observed for the next 6 or 24 hours.ResultsS/R caused the oxidation of hepatic glutathione and generated centrolobular leukocyte accumulation at 6 hours, followed by predominantly centrolobular hepatocellular injury at 24 hours. Each of these components was attenuated by PAF inhibition with WEB 2170, xanthine oxidase inhibition with allopurinol, antioxidant treatment with N-acetylcysteine, or severe leukopenia induced by vinblastine. In each case, the degree of leukocyte accumulation at 6 hours correlated with the hepatocellular injury seen at 24 hours. However, xanthine oxidase inhibition with allopurinol failed to attenuate further the small level of residual hepatocellular injury seen in leukopenic rats.ConclusionThese findings suggest that reactive oxidants generated by xanthine oxidase at reperfusion, stimulated by PAF, mediate hepatocellular injury by triggering leukocyte accumulation, primarily within the centrolobular sinusoids.