摘要：探讨重组杀菌／通透性增加蛋白(rBPI21)对内毒素休克中肝组织一氧化氮合酶(NOS)的影响及其意义。方法：大鼠腹腔注射大肠杆菌内毒素(15.0mg／kg)复制内毒素休克模型，动物随机分成正常对照组、内毒素休克组和rBPI21治疗组。检测肝组织NOS活性、三磷酸鸟苷环水解酶I(GTP-CHI)活性及生物喋呤含量，同时还观察肝脏微循环血流灌注量的改变。结果：内毒素攻击后肝组织诱生型NOS(iNOS)活性急剧升高(P＜0.01)，但原生型NOS(cNOS)活性变化不明显(P＞0.05)。rBPI21治疗可显著抑制iNOS活性，明显提高肝脏微循环灌注量(P＜0.01)；同时局部组织的GTP-CHI活性降低(P＜0.01)，生物喋呤含量也显著下降(P＜0.05)。结论：内毒素休克早期给予rBPI21能选择性抑制肝组织iNOS活性并改善局部微循环，其作用机理可能与降低组织GTP-CHI活性及其介导生物喋呤诱生有关。

The Effect of Recombinant Bactericidal／Permeability Increasing Protein on Hepatic Nitric Oxide Synthase Activity inv Rats after Endotoxic Shock.

yao Yongmjng,Peng Zhiqi,Dong Ning(Trauma Research Center,304th Hospital of PLA,Beijing(100037))

Abstract：To evaluate the potential effect of recombinant bactericidal／permeability increasing protein (rBPI21)on hepatic nitric oxide synthase(NOS)activity and its significance following endotoxic shock．Methods：SD rats were subjected to endotoxic shock induced by a bolus injection of lipopolysaccharide(15.0mg／kg，i.p.)．The animals were randomly divided into normal controls(n=10)，endotoxic shock group(n=20)and rBPI12-treated group(n=20)．Hepatic NOS，guanosine triphosphate cyclohydrolase I(GTP-CHI)activities,and biopterin levels were measured at various intervals．Also，hepatic microcirculatory perfusion was determined by laser Doppler flowmetry．Results：Following endotoxin challenge，hepatic inducible NOS(iNOS)activities were significantly elevated(P＜0.01)，while constitutive NOS(cNOS)activities showed no marked change at any time point(P＞0.05)．Treatment with rBPI21，significantly inhibited hepatic iNOS activities with improvement of microcirculatory perfusion．Local gTP-CHI activities and biopterin levels were much lower in rBPI21treated group than that in endotoxic shock group(P＜0.05～0.01)．Conclusions：Early treatment with rBPI21can selectively inhibit endotoxin-induced hepatic iNOS activity and improve local microcirculatory perfusion，probably through the down-regulation of gTP-CHI activity and biopterin formation in the liver．

Keywords：Septic shock Recombinant bactericidal／permeability increasing protein Nitric oxide synthase Biopterin Liver injury基金项目：本课题为国家重点基础发展规划项目(批准号：G1999054203)、国家自然科学基金(批准号：39870286)、军队杰出中青年人才专项基金(批准号：98J013)和中国工程院科技奖基金资助项目参考文献：

［1］姚咏明，吴 叶，盛志勇．杀菌／通透性增加蛋白防治革兰氏阴性菌脓毒症的研究现状．中国危重病急救医学,1997,9:759．

［2］姚咏明，彭志齐，常国友，等．杀菌／通透性增加蛋白对内毒素休克大鼠微循环灌注的保护作用．中华麻醉学杂志,1999,19:410．

［3］Fukushim T，Nixon JC．Analysis Of reduced forms of biopterin in biological tissues and fluids．Anal Biochem,1980,102:176.

［4］Kilbourn R．Nitric oxide synthase inhibitors——A mechanism-based treatment of septic shock．Crit Care Med,1999,27:857．

［5］姚咏明，赵晓东，于 燕，等．内毒素休克大鼠组织生物喋呤及其合成限速酶基因表达的改变．中华外科杂志,1999,37:267．

［6］李红云，姚咏明，施志国．生物喋呤的生物学效应及其在脓毒症中的作用．生理科学进展,1999,30:303．

收稿日期：1999-11-08