Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan.
Shock. 2011 Mar;35(3):289-92. doi: 10.1097/SHK.0b013e3181f48987.
Septic shock is characterized by systemic inflammation and can lead to hemorrhage and necrosis in multiple organs. Septic shock is one of the leading causes of death. Studies have reported that septic shock is strongly associated with coagulation abnormality. The adenosine diphosphate (ADP) receptor antagonist, clopidogrel sulfate (CS), inhibits platelet function. Thus, we hypothesized that CS could inhibit LPS-induced systemic inflammation in a rat model. Male Wistar rats weighing 250 to 300 g received an LPS injection, followed 6 h later by filtration leukocytapheresis or mock treatment for 30 min under sevoflurane anesthesia. Five days before LPS injection, rats were given an oral dose of water or CS (10 mg/kg body weight). Levels of proinflammatory markers were determined in serum and tissue samples, and high-mobility group box 1 (HMGB1) expression was evaluated in lung and liver tissues. Compared with LPS-treated rats, induction of cytokines (IL-6 and TNF-α) was reduced in rats pretreated with CS. In addition, histological changes observed in lung and liver tissue samples of LPS-treated rats were attenuated in CS-pretreated rats. Clopidogrel sulfate pretreatment also reduced LPS-induced HMGB1 expression in lung and liver tissues. Collectively, our findings demonstrate that CS pretreatment may have value as a new therapeutic tool against systemic inflammation.
感染性休克的特征是全身炎症，并可导致多个器官出血和坏死。感染性休克是导致死亡的主要原因之一。研究报告称，感染性休克与凝血异常密切相关。二磷酸腺苷（ADP）受体拮抗剂氯吡格雷硫酸酯（CS）可抑制血小板功能。因此，我们假设 CS 可抑制 LPS 诱导的大鼠模型中的全身炎症。雄性 Wistar 大鼠体重 250-300g，给予 LPS 注射，6 小时后，在七氟醚麻醉下进行过滤白细胞清除术或模拟治疗 30 分钟。在 LPS 注射前 5 天，大鼠给予水或 CS（10mg/kg 体重）口服剂量。测定血清和组织样本中促炎标志物的水平，并评估肺和肝组织中高迁移率族蛋白 1（HMGB1）的表达。与 LPS 处理的大鼠相比，CS 预处理大鼠诱导的细胞因子（IL-6 和 TNF-α）减少。此外，在 CS 预处理大鼠中，观察到 LPS 处理的大鼠肺和肝组织样本中的组织学变化得到缓解。CS 预处理还降低了 LPS 诱导的肺和肝组织中 HMGB1 的表达。总之，我们的研究结果表明，CS 预处理可能是一种针对全身炎症的新的治疗工具。
