白细胞去除对内毒素血症犬凝血功能及肺损伤的影响

Changes of coagulation and lung injury in response to leukocytapheresis in endotoxemia dog

目的观察白细胞去除后凝血纤溶系统的变化，探讨这一变化对肺损伤的影响及其可能机制。方法用内毒素（LPS）2mg／kg建立内毒素血症犬模型。30只雄性杂种犬采用随机数字表法分为LPS组（L组）、伪白细胞去除对照组（S组）、白细胞去除治疗组（T组），每组10只。L组只给予LPS输注，不行白细胞去除（leukocytapheresis，LCAP）；S组在LPS输注后12～14h间行伪白细胞去除；T组在LPS输注后12—14h间行LCAP。动态观察每组动物外周血活化蛋白C（activated protein C，APC）、可溶性血栓调节蛋白（soluble thrombomodulin，sTM）及纤溶酶原激活物抑制物-1（plasminogen activator inhibitor-1，PAI—1）在输注LPS前及输注后2，6，12，14，16，24及36h的变化。结果（1）T组动物在14，16h时血清APC水平[（50．805±4．422）μg／ml、（40，480±2．993）μg/ml]分别高于L组[（45．881±4．024）μg/ml、（35．935±4．057）μg／ml]（P〈0．05）；（2）T组在14，16h时sTM水平[（9．688±0．914）μg／ml、（10．492±0．865）μg/ml]分别低于L组[（11．005±0．854）μg/ml、（12．04±0．954）μg/ml]（P〈0．05）；（3）T组在14，16h时PAI-1水平显著低于L组（P〈0．05）；（4）T组急性肺损伤发生率显著低于L组（2／10：7／10，P〈0．05）。结论LPS诱导的内毒素血症早期存在凝血纤溶功能异常，白细胞去除能改善凝血纤溶功能，可能是白细胞去除减少急性肺损伤发生率的作用机制之一。

Objective To observe the effect of leukocytapheresis （LCAP） on the coagulation, fibrinolysis system and lung injury in the endotoxemia dog and explore the mechanism in the endotoxin-in- duced lung injury dog. Methods Endotoxemia-induced model in dogs was established by administration of lipopolysaecharide （LPS, 2 mg/kg）. Separation of the leucocytes was performed with the automa- ted continuous flow blood cell separators. A total of 30 male mongrel dogs were randomly divided into LPS group （group L, only injected with LPS, with no LCAP） , sham LCAP group （group S, received sham LCAP at 12-14 hours after administration of LPS） and LCAP treatment group （ group T, received LCAP at 12-14 hours after administration of LPS） , 10 dogs per group. The dynamic changes of the activated pro- tein C （APC） , soluble thrombomodulin and plasminogen activator inhibitor-1 in the serum were measured at 0 hour before LPS administration, at 2, 6, 12, 14, 16, 24 and 36 hours after administration of LPS. Results Through LCAP, there found the following four results ： （ 1 ） the APC level in the serum of the group T was （50.805 ±4.422）μg/ml and （40. 480 ±2. 993）μg/ml at 14 hours and 16 hours respectively, which were significantly higher than （45. 881 ±4.024） μg/ml and （35. 935 ± 4. 057） μg/rnl in the group L （P 〈 0. 05 ）. （2） The expressions of soluble thrombomodulin in the group T was （9. 688 ±0.914）μg/ml and （10.492 ±0. 865）μg/ml at 14 hours and 16 hours respectively, which was statistically lower than （11. 005 ± 0. 854 ） μg/ml and （12.04 ± 0. 954） μg/ml in the group L （P 〈 0.05 ）. （3） The level of plasminogen activator inhibitor -1 in the group T was lower than that in the group L at 14 and 16 hours （P 〈 0.05 ）. （4） As a result, the incidence rate of acute lung injury of the dogs in the group T was statistically lower than that in the group L （ALI/ARDS occurred in 2 and 7 dogs of the groups T and L respectively within 36 hours after infusion of LPS, P 〈 0.05 ）. Conclusions At the early period of endotoxemia, the dogs manifest abnormal coagulation and fibrinolysis function. LCAP can decrease the incidence of acute lung injury partly durtly to its role in improving the function of coagulation and fibrinolysis.