Matsumura F, Yamaguchi Y, Goto M, Ichiguchi O, Akizuki E, Matsuda T, Okabe K, Liang J, Ohshiro H, Iwamoto T, Yamada S, Mori K, Ogawa M
Department of Surgery II, Kumamoto University Medical School, Kumamoto, Japan.
Hepatology. 1998 Dec;28(6):1578-87. doi: 10.1002/hep.510280618.
We investigated the effects of the xanthine oxidase inhibitor, BOF-4272, on the production of cytokine-induced neutrophil chemoattractant (CINC) following reperfusion injury in rat liver. Ischemia was induced for 30 minutes by portal vein occlusion. Animals were pretreated with intravenous injection of BOF-4272 (1 mg/kg) or heparin (50 U/kg) 5 minutes before vascular clamp. Both BOF-4272 and heparin limited increases in the chemoattractant compared with nonpretreated rats. Pretreatment with BOF-4272 plus heparin resulted in an additive effect. Most cells immunostained for chemoattractant were macrophages in sinusoids. In vitro chemoattractant production by Kupffer cells isolated from animals pretreated with heparin or BOF-4272 was significantly lower than by Kupffer cells from nonpretreated animals. Expression of transcripts in liver for chemoattractant peaked 3 hours after reperfusion in nonpretreated animals, while pretreatment with heparin or BOF-4272 significantly decreased chemoattractant mRNA levels. In vitro chemoattractant transcription and production could be induced in naive Kupffer cells by hypoxanthine and xanthine oxidase, but BOF-4272 prevented these increases. We conclude that Kupffer cells release chemoattractant in response to oxygen radicals reducible by xanthine oxidase inhibition.
我们研究了黄嘌呤氧化酶抑制剂BOF - 4272对大鼠肝脏再灌注损伤后细胞因子诱导的中性粒细胞趋化因子（CINC）产生的影响。通过门静脉闭塞诱导缺血30分钟。在血管夹闭前5分钟，对动物进行静脉注射BOF - 4272（1毫克/千克）或肝素（50单位/千克）预处理。与未预处理的大鼠相比，BOF - 4272和肝素均限制了趋化因子的增加。BOF - 4272加肝素预处理产生了相加效应。大多数趋化因子免疫染色阳性的细胞是肝血窦中的巨噬细胞。从用肝素或BOF - 4272预处理的动物中分离出的库普弗细胞的体外趋化因子产生显著低于未预处理动物的库普弗细胞。在未预处理的动物中，肝脏中趋化因子转录本的表达在再灌注后3小时达到峰值，而肝素或BOF - 4272预处理显著降低了趋化因子mRNA水平。次黄嘌呤和黄嘌呤氧化酶可诱导未激活的库普弗细胞进行体外趋化因子转录和产生，但BOF - 4272可阻止这些增加。我们得出结论，库普弗细胞会因黄嘌呤氧化酶抑制可还原的氧自由基而释放趋化因子。
