ADENOSINE DIPHOSPHATE RECEPTOR ANTAGONIST CLOPIDOGREL SULFATE ATTENUATES LPS-INDUCED SYSTEMIC INFLAMMATION IN A RAT MODEL
ADENOSINE DIPHOSPHATE RECEPTOR ANTAGONIST CLOPIDOGREL SULFATE ATTENUATES LPS-INDUCED SYSTEMIC INFLAMMATION IN A RAT MODEL
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DOI：
10.1097/shk.0b013e3181f48987
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发表时间：
2011-03-01
期刊：
影响因子：
3.1
通讯作者：
Noguchi, Takayuki
中科院分区：
文献类型：
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作者：
Hagiwara, Satoshi;Iwasaka, Hideo;Noguchi, Takayuki
感染性休克的特点是全身性炎症，可导致多器官出血和坏死。感染性休克是导致死亡的主要原因之一。有研究报道脓毒性休克与凝血功能异常密切相关。二磷酸腺苷（ADP）受体拮抗剂硫酸氯吡格雷（CS）抑制血小板功能。因此，我们假设CS可以抑制lps诱导的大鼠全身炎症。体重250 ~ 300 g的雄性Wistar大鼠注射LPS， 6 h后进行滤过性白细胞摘除术或七氟醚麻醉模拟治疗30 min。在LPS注射前5天，给大鼠口服水或CS （10 mg/kg体重）。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组盒1 （HMGB1）的表达。与lps处理的大鼠相比，CS预处理的大鼠细胞因子（IL-6和tnf - α）的诱导减少。此外，lps预处理大鼠的肺和肝组织样本的组织学变化在cs预处理大鼠中有所减弱。硫酸氯吡格雷预处理也能降低lps诱导的肺和肝组织HMGB1的表达。总的来说，我们的研究结果表明，CS预处理可能具有作为对抗全身性炎症的新治疗工具的价值。
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-alpha) 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.