烟碱对肠缺血再灌注损伤大鼠凝血功能的影响

目的 观察胆碱能激动剂烟碱对大鼠肠缺血再灌注损伤后凝血功能的影响。方法 选取32只体质量250~300g雄性健康SD大鼠，采用随机数字表法将它们分为四组（n=8）：假手术（sham operation，S）组、肠缺血再灌注（ischemia-reperfusion，IR）组、烟碱（nicotine，NIC）组、α7烟碱型乙酰胆碱受体（α7 nicotinic acetylcholine receptor，α7nAchR）拮抗剂α-银环蛇毒素（α-bungarotoxin，α-BGT）组。大鼠肠缺血再灌注损伤模型采取肠系膜上动脉夹闭45min后恢复再灌注120min的方法建立。α-BGT组在肠系膜上动脉夹闭前45min和30min分别腹腔注射α-BGT 1μg/kg,烟碱400μg/kg；NIC组用等容量生理盐水替代α-BGT, S组和IR组用等容量生理盐水替代α-BGT和烟碱，其余均同α-BGT组。在大鼠恢复再灌注120min后经腹主动脉取血样，检测血浆肿瘤坏死因子-α（plasma tumor necrosis factor，TNF-α）、组织因子（tissue factor，TF）、抗凝血酶（antithrombin，AT）、组织型纤溶酶原激活物（tissue plasminogen activator，tPA）、纤溶酶原激活物抑制物-1（fiber plasminogen activator inhibitor-1，PAI-1）、D-二聚体水平和血小板计数（platelet count，PLT）。取远端回肠采用Chiu评分法评估小肠组织受损程度。结果 与S组和NIC组比较，IR组和α-BGT组血浆TNF-α、TF、tPA、PAI-1和D-二聚体水平均出现显剧升高，血浆AT水平下降，血小板计数下降（P<0.05），小肠组织Chiu评分增加（P<0.05）。结论 烟碱能够抑制大鼠肠缺血再灌注损伤导致的凝血功能过度激活；其作用机制可能为外周α7烟碱型乙酰胆碱受体结合，引起胆碱能抗炎通路的激活,进而导致促炎性细胞因子的释放减少，从而减轻内皮细胞的损伤。

Effect of nicotine on coagulation and fibrinolysis in intestinal ischemia-reperfusion injury rats

Objective To investigate the effect of nicotine on coagulation in intestinal ischemia-reperfusion injury rats. Methods 32 male Sprague-dawley rats, weighing 250-300g, were randomly divided into 4 groups (n=8): sham operation group (S), intestinal ischemia-reperfusion (IR) group, nicotine (NIC) group, α7 nicotinic acetylcholine receptor (α7nAchR) antagonist group α-bungarotoxin (α-BGT) group. Intestinal IR was induced by clamping superior mesenteric artery for 45min and 120min of reperfusion. In group NIC nicotine 400μg/kg was injected intraperitoneally at 30min before superior mesenteric artery occlusion. In group α-BGT 1μg/kg was injected intraperitoneally at 15min before superior mesenteric artery occlusion. Plasma tumor necrosis factor-α (TNF-α), tissue factor (TF), antithrombin (AT), tissue plasminogen activator (tPA), fiber plasminogen activator inhibitor-1 (PAI-1), D-dimer levels and platelet count (PLT) were measured after 120min reperfusion. Chiu’s count was used to assess the changes in intestinal mucosal pathlolgical morphology. Results Compared with group S and group NIC, the plasma TNF-α，TF, tPA, PAI-1 and D-dimer levels were significantly increased, and plasma AT level and platelet count were significantly decreased, in group IR and group α-BGT(P<0.05)，Chiu’s scores were significantly increased(P<0.05). Conclusion Nicotine can inhibit the excessive activation of coagulation function in intestinal ischemia-reperfusion injury rats. Its mechanism may be related to activation of cholinergic antiinflammatory pathway, reducing the release of pro-inflammatory cytokines thereby reducing endothelial cell injury.