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烟碱对肠缺血再灌注损伤大鼠凝血功能的影响OA

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

中文摘要英文摘要

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.

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.

汪海松;徐林梅;陈振毅;高海鹰;蔡东妙

厦门大学附属第一医院麻醉科,福建厦门 361003

临床医学

肠缺血再灌注损伤血液凝固烟碱

Intestinal ischemia-reperfusion injuryBlood coagulationNicotine

《中国现代医生》 2024 (014)

46-48,64 / 4

福建省厦门市自然科学基金项目(3502Z202373094)

10.3969/j.issn.1673-9701.2024.14.010

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