杀菌/通透性增加蛋白防治创伤后内毒素血症及其增敏效应

Effect of Recombinant Bactericidal/PermeabilityIncreasingProtein on Traumainduced Endotoxemia and Its Mechanisms

目的：探讨脂多糖结合蛋白（ＬＢＰ）在严重创伤后肠源性内毒素血症诱发多器官损害中的作用及杀菌／通透性增加蛋白（ＢＰＩ）的防治效应。方法：采用大鼠重度失血性休克（３０～３５ｍｍＨｇ，１８０ｍｉｎ）、３５％Ⅲ°烫伤模型，观察应用重组ＢＰＩ（ｒＢＰＩ２１）对血浆内毒素含量，肺、肝、肠、肾等组织ＬＢＰｍＲＮＡ表达，多器官病理改变及动物存活率的影响。结果：给予ｒＢＰＩ２１可完全防止休克所致内毒素血症的发生，血浆内毒素峰值显著低于对照组〔７４．０±２２．５）对（１３．８±６．８）ｐｇ／ｍｌ，Ｐ＜０．０５。〕烫伤８小时治疗组血浆内毒素均值降低４２．４％。同时，ｒＢＰＩ２１处理不同程度地抑制动物肺、肝、肠、肾等组织ＬＢＰｍＲＮＡ表达水平（Ｐ＜０．０５～０．０１）。病理形态学检查显示治疗组严重休克后脏器损害明显减轻，动物４８小时存活率提高３１．３百分点（６８．８％对３７．５％，Ｐ＝０．０８）。结论：严重创伤早期应用ｒＢＰＩ２１能减轻内毒素血症诱发的多器官损害及改善动物预后。

おbjective: To investigate the potential role of lipopolysaccharidebinding protein (LBP) in the pathogenesis of endotoxemiamediated multiple organ dysfunction syndrome, and the effect of recombinant bactericidal/permeabilityincreasing protein (rBPI) following severe trauma. Methods: Rats were subjected to prolonged hemorrhagic shock (30～35 mmHg 180 min) and 35% body surface are a fullthickness thermal injury. Plasma endotoxin, tissue LBP mRNA expression, and morphological evaluation were determined in animals with and without rBPI21 treatment. Results: Treatment with rBPI21 resulted in almost neutralization of plasma endotoxin levels following hemorrhagic shock and resuscitation 〔control vs. treatment group: (740±225) vs.(138±68) pg/ml,P<005〕, and blunted the elevation of circulating endotoxin at 8 hours after thermal injury compared with the controls. Also, tissue LBP mRNA expression in varous organs was markedly inhibited by treatment with rBPI21 secondary to acute insults (P<005～001).Moreover, microscopic histopathologic examination revealed relatively minor damage to vital organs in the treatment group, and the 48hour survival rate was higher in rBPI21treated group than in the control group (688% vs. 375%, P=008). Conclusion: Early treatment with rBPI21 could attenuate endotoxemiamediated multiple organ damage and reduce 48hour mortality resulting from severe hemorrhage/burns, which might be associated with the downregulation effects of tissue LBP gene expression by use of rBPI21.