Failure of Kupffer cell blockade to prevent disseminated intravascular coagulation in endotoxemic rats despite improved survival
Failure of Kupffer cell blockade to prevent disseminated intravascular coagulation in endotoxemic rats despite improved survival
复制标题
DOI：
10.1007/s004230050095
复制
发表时间：
1998-03-01
影响因子：
2.3
通讯作者：
Messmer, K
中科院分区：
文献类型：
--
作者：
Ruttinger, D;Vollmar, B;Messmer, K
目的：研究阻断肝巨噬细胞(Kupffer cell，KC)吞噬功能的试剂氯化GdCl3(GdCl3)对致死剂量的大肠杆菌脂多糖(LPS，10 mg/kg体重)所致大鼠凝血系统及死亡率的影响。方法：用GdCl3(10 mg/kg，静脉注射，内毒素暴露前48h和24 h)或生理盐水对大鼠进行预处理。在注射大肠杆菌内毒素的早期(1h)和晚期(16h)监测各种凝血指标，如活化部分凝血酶原时间(APTT)、纤维蛋白原、系统血小板计数、抗凝血酶III(AT III)以及因子V、VII和XII的活性。结果：内毒素引起弥散性血管内凝血(DIC)，16h内死亡率为47%，GdCl3阻断KC可完全消除内毒素相关的死亡率(0%)。然而，尽管存活率有所提高，GdCl3仍未能预防DIG的实验室和临床迹象。GdCl3本身甚至会导致凝血和纤溶障碍。结论：上述结果证实了GdCl3对实验性内毒素血症的保护作用。然而，本研究并不支持将DIC作为脓毒症和感染性休克预后的有力标准。此外，这些结果表明KC在内毒素介导的凝血激活中起到了很小的作用，并表明KC参与了与内毒素相关的致死性，而不依赖于凝血系统。
Objective: Studies were conducted to evaluate the impact of gadolinium chloride (GdCl3), an agent which blocks the phagocytosis of liver macrophages (Kupffer cells, KC), on the coagulation system and on mortality in a model of rats subjected to a lethal dose of Escherichia coli lipopolysaccharide (LPS) (10 mg/kg body weight, intravenously). Methods: Rats were either pretreated with GdCl3 (10 mg/kg, i.v., 48 h and 24 h prior to LPS exposure) or saline vehicle. A variety of coagulation parameters such as activated partial prothrombin time (aPTT), fibrinogen, systemic platelet count, antithrombin III (AT III), and activities of factors V, VII, and XII were monitored in the early (1 h) and late time course (16 h) following administration of E. coli LPS. Results: The administration of LPS resulted in the development of disseminated intravascular coagulation (DIC) and was associated with a mortality rate of 47% within 16 h. Blockade of KC by GdCl3 completely abolished LPS-related mortality (0%). However, despite improved survival, GdCl3 failed to prevent laboratory and clinical signs of DIG. GdCl3 per se even contributed to coagulatory and fibrinolytic disorders. Conclusion: These results confirm reports on the protective potential of GdCl3 pretreatment in experimental endotoxemia. However, the present study does not support the concept of DIC as a strong prognostic criterion for the outcome of sepsis and septic shock. Furthermore, the results presented suggest a minor role for KC in LPS-mediated activation of coagulation and indicate an involvement of KC in LPS-associated lethality independent of the coagulation system.