高容量血液滤过防治猪多脏器功能障碍综合征过程中TNF-α和HMGB1的变化

Changes of plasma TNF-α and HMGB1 in minipigs with multiple organ dysfunction treated with high volume hemofiltration

目的:观察高容量血液滤过(HVHF)防治多脏器功能障碍综合征(MODS)过程中肿瘤坏死因子α(TNF-α)和高迁移率族蛋白1(HMGB1)的变化。方法:19只健康雄性家猪随机分成MODS组(n=9)和HVHF组(n=10),均采用失血性休克复苏+内毒素血症复合因素建立猪MODS模型,HVHF组动物注射内毒素后采用F50聚砜膜滤器予血液滤过,超滤量3 L/h。观察2组动物处死前主要器官功能指标,记录MODS的发生率与病死率。2组均于放血前、内毒素注射前、内毒素注射后1h、24h、48h及96h留取血标本,采用ELISA法测定血浆TNF-α含量,Western blotting法检测血浆HMGB1蛋白含量。结果:2组动物处死前主要器官功能明显改善。HVHF组MODS发生率与病死率均低于MODS组(P<0.05)。MODS组TNF-α和HMGB1均明显升高,HMGB1较TNF-α分泌高峰延迟,持续时间较长;与MODS组相比,HVHF组HMGB1蛋白相对于基础值水平升高幅度明显降低,TNF-α各时间点均有不同程度下降。结论:过度的炎症反应是MODS发生的本质原因之一,HVHF能够削弱血循环中TNF-α和HMGB1等炎症介质的峰值浓度,有效遏制过度的炎症反应,从而起到防治MODS的作用。

Aim： To observe the changes of plasma tumor necrosis factor-alpha （TNF-α） and high mobility group-1 protein（HMGB1 ） in minipigs with multiple organ dysfuncition （MODS） treated with high volume hemofiltration（HVHF）. Methods： Nineteen healthy male minipigs were randomly divided into MODS group and HVHF group. Double-hit method was used to establish the porcine MODS model. The animals in HVHF group underwent prophylactic HVHF （3 L/h） after injection of endotoxin. F50 polysulfone membrane filter was used. Plasma levels of TNF-α and HMGB1 at different time points were detected by enzyme-linked immunosorbent assay（ELISA） and Western blotting, respectively, Results： The mobidity of MODS in group HVHF was lower than that in group MODS（P 〈0.05）. Main organs＇ function was improved by HVHF. The plasma levels of TNF-α and HMGB1 obviously elevated in MODS group after the endotoxin injection, and HMGB 1 achieved the peak value later than TNF-α, but it also dropped later; in group HVHF, the increase of HMGB1 com- pared with base level was lower than that in group MODS, and the plasma levels of TNF-α were obviously decreased at vari- ous time points. Conclusion ： Excessive inflammatory response may be the essential pathogenesis of MODS. HVHF can cut down the peak value of inflammatory cytokines including TNF-α and HMGB1 protein, which can prevent and treat MODS through restraining excessive inflammatory response.