天津医药

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双联抗血小板聚集药物致小肠损伤的动物实验研究*

刘霞1,张志广2,李熳3,张雪莲1   

  1. 1. 天津医科大学第二医院消化内科
    2. 天津医大二院消化科
    3. 天津医科大学第二医院
  • 收稿日期:2013-06-18 修回日期:2013-10-14 出版日期:2014-02-15 发布日期:2014-02-15
  • 通讯作者: 刘霞

The Animal Experiment Research of Dual Antiplatelet Drugs Induced Intestinal Damage

  • Received:2013-06-18 Revised:2013-10-14 Published:2014-02-15 Online:2014-02-15

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摘要： 　　　【摘要】 目的 探讨双联抗血小板药物对大鼠小肠损伤的情况及其可能发生的机制。方法 SD大鼠80只，随机分为阴性对照组、阿司匹林组、氯吡格雷组、阿司匹林联合氯吡格雷组（以下简称双抗组），每组20只，分别予生理盐水、阿司匹林(10.41mg/kg.d)、氯吡格雷(7.81mg/kg.d)、阿司匹林联合氯吡格雷灌胃每天一次，共14天。所有大鼠于末次给药后手术，观察小肠损伤情况，取空肠液行细菌培养，EB行小肠通透性检测，按照Chiu CJ方法进行小肠黏膜病理损伤评分（HE染色法）。结果 1.各实验组大鼠小肠黏膜均出现不同程度损伤，病理损伤评分均高于阴性对照组（P<0.05），且以双抗组最高；2.与对照组相比，各实验组大鼠小肠通透性均明显增高（P<0.05），双抗组高于阿司匹林组及氯吡格雷组（130.533±29.631vs90.965±3.765vs66.800±4.853，P=0.000)；3.双抗组大鼠空肠液细菌总量较对照组明显增多（61924.805±1751.159vs18154.280±1153.376，P=0.000），肠杆菌与肠球菌比例较对照组明显下降（0.220±0.089vs1.007±0.148，P=0.000）。结论 常规剂量双联抗血小板药物的使用较单一用药造成大鼠小肠损伤程度加重，肠道细菌数量增多，菌群失调、小肠通透性的增高可能参与了小肠黏膜损伤的过程。

关键词: 双联抗血小板药物, 小肠损伤, 通透性, 菌群失调

Abstract: 【Abstract】 Objective To investigate the effect and its possible mechanism on the digestive tract in rats of dual antiplatelet drugs .Methods 80 SD rats were randomly allocated into four groups:these experiment groups to give clopidogrel (7.81mg/kg.d,n=20),aspirin (10.41mg/kg.d,n=20) and clopidogrel combined aspirin (hereafter referred to dual antiplatelet,n=20) respectively. Each group had the intragastric administration once daily,blank group will give normal saline(n=20),meanwhile. All rats received operation after the final intragastric administration,then observed small intestinal injury,bacterial culture of jejunal fluid,small intestinal permeability test through EB,estimated the injury degree of small intestinal mucosa by HE staining.Results 1.Each experiment group rats’small intestinal mucosa have different degree of damage ,and pathological lesions were higher than the negative control group（P<0.05）,moreover,the dual antiplatelet group was the highest;2.Each experiment group rats’ small intestinal permeability increased obviously compared with the control group（P<0.05）,and the dual antiplatelet group was higher than both the aspirin group and the clopidogrel group （130.533±29.631vs90.965±3.765vs66.800±4.853,P=0.000)；3.The total bacteria of the dual antiplatelet group rats’ jejunal was apparently higher than the control group（61924.805±1751.159vs18154.280±1153.376,P=0.000）,and the ratio of enterobacterium and enterococcus decreased obviously in the dual antiplatelet group compared with the control group（0.220±0.089vs 1.007±0.148,P=0.000）.Conclusions Routine dose of dual antiplatelet drug aggravates the small intestinal injury degree of rats compared with a single drug. The increased intestinal bacteria ,dysbacteriosis, and increased small intestinal permeability may participate in the small intestinal mucosa damage process.

Key words: Dual antiplatelet drugs, Small intestinal injury, Permeability, Dysbacteriosis