烟碱对内毒素血症大鼠凝血功能的影响

目的 探讨烟碱对内毒素血症大鼠凝血功能的影响.方法 成年健康雄性SD大鼠96只,体重200～250 g,采用随机数字表法,将大鼠随机分为4组(n=24):生理盐水对照组(NS组)、内毒素组(LPS组)、烟碱组(NIC组)、α7烟碱型乙酰胆碱受体(α7nAchR)拮抗剂组(α-BGT组).LPS组、NIC 组和α-BGT组经股静脉注射脂多糖(LPS)10 mg/kg制备内毒素血症模型.α-BGT组于注射LPS前45min腹腔注射α-BGT 1μg/kg,注射α-BGT后15 min腹腔注射烟碱400 μg/kg.NIC组除用等容量生理盐水替代α-BGT外,余操作同α-BGT组.LPS组除用等容量生理盐水替代烟碱外,余操作同NIC组.NS组除用等容量生理盐水替代LPS外,余操作同LPS组.于注射LPS前、注射后2、4、6 h时采集腹主动脉血样,检测血浆凝血酶原时间(PT)、部分活化凝血活酶时间(APTT)、纤维蛋白原(Fib)、抗凝血酶(AT)、血管性血友病因子(vWF)、纤溶酶原激活物抑制物-1(PAI-1)、D-二聚体、肿瘤坏死因子-α(TNF-α)水平和血小板计数.结果 与NS组比较,LPS组和α-BGT组PT、APTT延长,血浆Fib、AT水平降低,血小板计数减少,血浆PAI-1、WF、D-二聚体与TNF-α水平升高(P＜0.05).与LPS组比较,NIC组PT、APTT缩短,血浆Fib和AT水平升高,血小板计数增加,血浆PAI-1、vWF、D-二聚体和TNF-α水平降低(P＜0.05).与NIC组比较,α-BGT组PT和APTT延长,血浆Fib和AT水平降低,血小板计数减少,血浆PAI-1、vWF、D-二聚体和TNF-α水平升高(P＜0.05).结论 烟碱可抑制内毒素血症大鼠过度激活的凝血反应,缓解抗凝血与纤维蛋白溶解功能的抑制状态,作用机制可能与其结合外周α7烟碱型乙酰胆碱受体激活胆碱能抗炎通路,从而减少促炎性细胞因子释放有关.

Abstract：

Objective To investigate the effect of nicotine on coagulation abnormalities in endotoxemic rats.Methods Ninety-six male SD rats weighing 200-250 g were randomly divided into 4 groups (n=24 each): group normal saline (group NS);group LPS;group nicotine(group NIC)and group α-bungarotoxin (α7 nicotinic acetylcholine receptor antagonist, group α-BGT) . Endotoxemia was induced by LPS 10 mg/kg injected via femoral vein in LPS, NIC and α-BGT groups. In group NIC nicotine 400 μg/kg was injected intraperitoneally at 30 min before LPS injection. In group α-BGT α-BGT 1 μg/kg was injected intraperitoneally at 15 min before intraperitoneal nicotine. Prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(Fib),antithrombin (AT),von Willebrand factor(vWF),plasminogen activator inhibitor-1(PAI-1),D-dimer,platelet count and TNF-α were measured before (baseline) and 2, 4 and 6 h after LPS injection.Results PT and APTT were significantly prolonged and plasma Fib and AT concentrations and platelet count were significantly decreased, while plasma PAI-1, D-dimer, vWF and TNF-α concentrations were significantly increased after LPS administration in group LPS as compared with group NS. Nitotine pretreatment significantly attenuated the LPS-induced changes in group NIC.The effect of nicotine was counteracted by α-BGT. Conclusion Nicotine can attenuate coagulation abnormalities induced by LPS by acting on α7 nicotinic acetylcholine receptor.

Effect of nicotine on coagulation abnormalities in endotoxemic rats

Objective To investigate the effect of nicotine on coagulation abnormalities in endotoxemic rats.Methods Ninety-six male SD rats weighing 200-250 g were randomly divided into 4 groups (n=24 each): group normal saline (group NS);group LPS;group nicotine(group NIC)and group α-bungarotoxin (α7 nicotinic acetylcholine receptor antagonist, group α-BGT) . Endotoxemia was induced by LPS 10 mg/kg injected via femoral vein in LPS, NIC and α-BGT groups. In group NIC nicotine 400 μg/kg was injected intraperitoneally at 30 min before LPS injection. In group α-BGT α-BGT 1 μg/kg was injected intraperitoneally at 15 min before intraperitoneal nicotine. Prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(Fib),antithrombin (AT),von Willebrand factor(vWF),plasminogen activator inhibitor-1(PAI-1),D-dimer,platelet count and TNF-α were measured before (baseline) and 2, 4 and 6 h after LPS injection.Results PT and APTT were significantly prolonged and plasma Fib and AT concentrations and platelet count were significantly decreased, while plasma PAI-1, D-dimer, vWF and TNF-α concentrations were significantly increased after LPS administration in group LPS as compared with group NS. Nitotine pretreatment significantly attenuated the LPS-induced changes in group NIC.The effect of nicotine was counteracted by α-BGT. Conclusion Nicotine can attenuate coagulation abnormalities induced by LPS by acting on α7 nicotinic acetylcholine receptor.