国际麻醉学与复苏杂志   2014, Issue (4): 11-11
    
胆碱酯酶抑制剂加兰他敏对脓毒症大鼠肠道屏障功能影响的实验研究
李光, 周青山, 李建国, 邹捍东, 余追1()
1.武汉大学人民医院
Effect of cholinesterase inhibitor galantamine on intestinal barrier function in rats with sepsis
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摘要:

目的 观察胆碱酯酶抑制剂加兰他敏对脓毒症大鼠黏膜肠道屏障功能的影响。 方法 Sprague-Dawley(SD)大鼠采用完全随机分组法分为5组(每组12只),即假手术(Sham)组,盲肠结扎穿孔(cecal ligation and puncture, CLP)组,CLP+加兰他敏组,迷走神经切除+CLP+加兰他敏组,迷走神经假切除+CLP+加兰他敏组,其中CLP组行盲肠结扎穿孔制备脓毒症模型,Sham组仅做开腹处理,加兰他敏于CLP模型制备成功后1 h行腹腔给药(5 mg/kg),右侧迷走神经切除于CLP模型制备前3 d。各组于术后12 h处死动物,取门静脉血检测内毒素水平,无菌取肠系膜淋巴结、脾、肝脏检测细菌移位情况,苏木精-伊红(hematoxylin-eosin, HE)染色并镜下观察回肠组织病理;单独设组观察各组动物一般情况及72 h生存率。 结果 CLP组大鼠生存率较Sham组明显降低(20% vs 100%),肠黏膜损害、血清内毒素及各脏器细菌移位均较Sham组明显增加(61.1% vs 11.1%,P<0.05)。加兰他敏治疗可显著改善CLP大鼠生存率(80%)、改善肠黏膜损伤,降低血清内毒素水平及细菌移位(27.8% vs 61.1%,P<0.05)。行迷走神经切除后,CLP大鼠对加兰他敏治疗无反应。 结论 加兰他敏可降低脓毒症大鼠肠道细菌移位,减轻肠黏膜损害,降低其死亡率,该作用可能系通过激活迷走神经而发挥作用。

关键词: 脓毒症;加兰他敏;肠黏膜屏障;细菌移位;胆碱能抗炎通路
Abstract:

Objective To investigate the effects of galantamine treatment on intestinal function in rats with sepsis. Methods Healthy male Sprague-Dawley(SD) rats were randomly divided into five experimental groups: Sham CLP group: rats were exposure abdominal cavity only. CLP group: cecal ligation and puncture (CLP) method to establish sepsis model. CLP+galantamine group: adminisration galantamine (5 mg/kg.ip) 1 h after CLP. vagotomy+CLP+galantamine group;right vagotomy 3 d before CLP. Sham vagotomy+CLP+galantamine group: Sham right vagotomy 3 d before CLP. Observed the survival rate of each group for 72 h. Rats were sacrificed at 12 h after CLP to observe the histopathological change of intestinal, and obtained the blood sample to test the endotoxin level, collected homogenated tissues of mesenteric lymph nodes,liver and spleen to determine bacterial translocation. Results The survival rate of rats in CLP group was significantly lower than in Sham CLP group (20% vs 100%), and the serum endotoxin level and bacterial translocation were higher in CLP group than in Sham CLP group(61.1% vs 11.1%, P<0.05), galantamine administration could obviously decrease endotoxin level and bacterial translocation(27.8% vs 61.1%, P<0.05), however, vagotomy before CLP operation could abolish the protect effects of galantamine (27.8% vs 61.1%, P<0.05). Conclusions Galantamine can reduce the degree of intestinal mucosa damage and bacterial translocation, increase the survival rate. Activation of vagus nerve might coutribute to these effect.

Key words: sepsis; galantamine;bacterial translocation;cholinergic anti-inflammation pathway