摘要
目的:观察延迟应用肿瘤坏死因子-α单抗(TNF MAb)对失血性休克所致血液动力学改变、多器官损伤及存活率的影响,并对其作用机理进行探讨。方法:采用大鼠重度失血性休克(4.00~4.66kPa,180分钟)、复苏模型,实验动物随机分成治疗组(复苏后注射TNF MAb 20.0mg/kg)和对照组(白蛋白,20.0mg/kg)。结果:延迟应用TNF单抗治疗后,心脏指数有所增高、外周血管阻力指数显著降低(P<0.05);肠、肺等多器官损害较对照组明显减轻(P<0.05)。同时,治疗组动物48小时存活率(73.3%)显著高于对照组(26.7%,P<0.05)。给予TNF MAb可不同程度地抑制组织TNF、脂多糖结合蛋白(LBP)mRNA表达(P<0.05~0.01)。结论:延迟应用TNF MAb可明显减轻重度休克所致多器官损害,并有效改善动物预后。其作用机理与TNF MAb广泛抑制不同组织TNF、LBP基因的表达有关。
To evaluate the effect of delayed treatment with monoclonal antibody to tumor necrosis factor-alpha (TNF-α MAb) on systemic hemodynamics and multiple organ dysfunction following prolonged hemorrhagic shock and resuscitation. Method: Adult male Sprague-Dawley rats were subjected to prolonged hemorrhagic shock (MAP of 4.00-4.66 kPa for 180 rain)followed by resuscitation over 50 min. The animals were treated intravenously with either TNF-α MAb (20.0 mg/kg) or the control protein(albumin,20.0 mg/kg)15 rain after the end of resuscitation(65 min after shock). Result: Compared to the albumin controls, delayed treatment with TNF-α MAh significantly reduced the total peripheral resistance index (P<0.05), tended to increase cardiac index, and provided remarkable protection from multiple organ damage, particularly in the lung and intestine (P<0.05). The 48-hour survival rate was significantly higher in the TNF-α MAb treatment group(73.3%) than in the control group (26.7%, P<0.05). TNF-α MAb administration markedly blunted the increase in various tissue TNF mRNA as well as lipopolysaccharide-binding protein(LBP) mRNA expression 2 hours after treatment (P<0.05-0.01). Conclusion: Prolonged hemorrhage leads to the gene expression and release of TNF, maybe contributing to the development of hemodynamic dysfunction, acute organ damage, and even to a fetal outcome. Anti-TNF treatment, even when starting after hemorrhage and resuscitation, attenuates hemorrhage-induced multiple organ dysfunction and improves the survival rate through inhibiting TNF and LBP mRNA expression secondary to severe hypovolemic shock.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
1998年第8期486-489,共4页
Chinese Journal of Anesthesiology
基金
全军"九五"医药卫生科研基金(编号96Q116)
关键词
出血性休克
抗体
肿瘤坏死因子
血液动力学
Shock, hemorrhagic Antibody, monoclonal Tumor necrosis factor Gene expression Hemodynamics Multiple organ failure