High‐mobility group box 1 protein promotes development of microvascular thrombosis in rats

摘要: Summary. Background: Sepsis is a life-threatening disorder resulting from systemic inflammatory and coagulatory responses to infection. High-mobility group box 1 protein (HMGB1), an abundant intranuclear protein, was recently identified as potent lethal mediator of sepsis. However, the precise mechanisms by which HMGB1 exerts its effects in sepsis have yet be confirmed. We reported that plasma levels correlated with disseminated intravascular coagulation (DIC) score, indicating might play important role pathogenesis DIC. Objectives: To investigate responsible for HMGB1, more specifically, explore on system. Methods: Rats were exposed thrombin or without survival analysis, pathologic analyses blood tests conducted. The cascade, anticoagulant pathways surface expression procoagulant molecules examined vitro. Results: Compared alone, combined administration resulted excessive fibrin deposition glomeruli, prolonged clotting times, increased mortality. In vitro, did not affect but inhibited C pathway mediated thrombin–thrombomodulin complex, stimulated tissue factor monocytes. Conclusions: These findings demonstrate vivo During sepsis, massive accumulation circulation would promote development