烟碱对内毒素血症大鼠凝血功能的影响  

Effect of nicotine on coagulation abnormalities in endotoxemic rats

作　　者：刘薇[1] 李建国[1] 宋学敏[1] 梁辉[1] 李光[1] 

机构地区：[1]武汉大学中南医院麻醉与重症医学研究中心,430071

出　　处：《中华麻醉学杂志》2011年第3期338-341,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（30972852）;武汉大学中南医院青年基金（200905）

摘　　要：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200～250g，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（a7nAchR）拮抗剂组（d．BGT组）。LPS组、NIC组和α-BGT组经股静脉注射脂多糖（LPs）10mg／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15rain腹腔注射烟碱400gg／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、6h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（Am）、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、APTY延长，血浆Fib、AT水平降低，血小板计数减少，血浆PAI-1、vWF、D-二聚体与TNF—α水平升高（P〈0．05）。与EPS组比较，NIC组PT、APTY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组胛和APIT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。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 （APTF）, fibrinogen （Fib）, antithrombin （AT）, van Willebrand factor （vWF）, plasminogen activator inhibitor-1 （PAl-1）, D-dimer, platelet count and TNF-α were measured before （baseline） and 2, 4 and 6 h after LPS injection. Results PT and APTF were significandy 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 aeetylcholine receptor.

关 键 词：胆碱能药 内毒素血症 血液凝固试验 

分 类 号：R965[医药卫生—药理学]