重组杀菌/通透性增加蛋白对内毒素休克中肝脏一氧化氮合酶的影响  

The Effect of Recombinant Bactericidal/ Permeability Increasing Protein on Hopatic Nitric Oxide Synthase Activity in Rats after Endotoxic Shock

作　　者：姚咏明[1] 彭志齐[2] 董宁[1] 于燕[1] 盛志勇[1] 

机构地区：[1]中国人民解放军第三O四医院创伤外科中心,100037 [2]中国人民解放军南京军事理工大学医院,210007

出　　处：《外科理论与实践》2000年第2期91-93,共3页Journal of Surgery Concepts & Practice

基　　金：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

摘　　要：目的：探讨重组杀菌／通透性增加蛋白（ｒＢＰＩ_(２１)）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 ｒＢＰＩ_(２１)治疗组。检测肝组织ＮＯＳ活性、三磷酸鸟苷环水解酶１（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）。 ｒＢＰＩ_(２１)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Ｆ降（Ｐ＜０.０５）。结论：内毒素休克早期给予ｒＢＰＩ_(２１)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。To evaluate the potential effect of recombinant bactericidal/permeability increasing protein (rBPI_(21)) 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 rBPI_12-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 rBPI21 treated group than that in endotoxic shock group(p<0.05-0.01). Conclusions: Early treatment with rBPI_(21) can 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.

关 键 词：内毒素休克 rBPI21 一氧化氮合酶 肝损害 

分 类 号：R605[医药卫生—外科学]