摘要
目的:观察阿司匹林和氯吡格雷联合应用对实验性急性心肌梗死(AMI)大鼠胃黏膜损伤的作用及微循环的影响。方法:SD大鼠60只,麻醉后结扎左冠状动脉前降支复制AMI模型,成模大鼠随机分为4组:(1)模型对照组(AMI组):蒸馏水(5ml/kg/天)灌胃;(2)阿司匹林组(AMI+阿司匹林组):阿司匹林(9mg/kg/天)灌胃;(3)氯吡格雷组(AMI+氯吡格雷组):氯吡格雷(6.75mg/kg/天)灌胃;(4)双联抗(阿司匹林和氯吡格雷)组(AMI+双联抗组):阿司匹林(9mg/kg/天)和氯吡格雷(6.75mg/kg/天)混悬液灌胃;另设假手术组(只穿刺不结扎冠脉,其余处理方法同模型对照组)作为对照。每组12只,雌雄各半。连续灌胃28天,次日麻醉后剖腹暴露胃黏膜,采用微循环观测系统观察恒温状态下各组大鼠胃黏膜微循环的毛细血管管径、数量、血流状态。同时取腹主动脉血,放射免疫法测定其6-酮-前列腺素F1α(6-keto-PGF_(1α))和血栓烷B_2(TXB_2)含量。之后处死大鼠摘取胃体,解剖显微镜下计数胃黏膜出血点并行Guth评分,HE染色观察胃组织病理学形态并行Whittle评分评价胃黏膜损伤程度。结果:与假手术组比较,AMI+阿司匹林组大鼠胃黏膜损伤程度明显,胃黏膜微循环受累,血管扩张,管壁变薄,排列紊乱(P<0.05);AMI+双联抗组胃黏膜损伤程度加重,胃黏膜微血管扩张、通透性增强,毛细血管交集数减少(P<0.05)。与假手术组比较,AMI组胃黏膜毛细血管数量增加(P<0.05)。与AMI组比较,AMI+阿司匹林组、AMI+双联抗组大鼠胃黏膜集合毛细血管管径显著增加(P<0.01),AMI+双联抗组毛细血管交集数减少(P<0.05)、毛细血管数量显著增加(P<0.01)。与假手术组比较,AMI组大鼠6-keto-PGF_(1α)水平显著下降(P<0.01),AMI+双联抗组、AMI+阿司匹林组和AMI+氯吡格雷组6-keto-PGF_(1α)和TXB_2水平均有不同程度降低(P<0.05,P<0.01)。与AMI组大鼠比较,给药各组6-keto-PGF_(1α)水平无明显变化(P>0.05),TXB_2水平明显降低(P<0.01)。结论:阿司匹林和氯吡格雷联用可加重AMI大鼠胃黏膜损伤,其机制可能与血液6-keto-PGF_(1α)与TXB_2水平降低和失衡,以及胃黏膜微循环障碍有关。
Objective： To observe the microcirculation change after gastric mucosas injury caused by aspirin and clopidogrel on rats with acute myocardial infarction（AMI） which was induced by ligating the left anterior descending coronary. Method： 60 SD rats with model establishment were randomly divided into 5 groups, 12 rats in each group, half male and half female. They were： （1） model group （AMI）which distilled water was given 2ml/（kg · d） ; （2） aspirin group（AMI＋ aspirin） which aspirin was given 9mg/（kg ·d） ; （3） clopidogrel group （AMI＋ clopidogrel） which elopidogrel was given 6.75mg/（kg · d） ; （4） aspirin＋clopidogrel group（AMI＋ aspirin＋ clopidogrel） which both of aspirin and clopidogrel were given; （5） sham group （the suture was penetrated around the left anterior descending coronary artery, but not tied） which distilled water was given 2ml/（kg ·d）. After continuous intragastric administration of 4 weeks, the gastric mucosa was exposed by cutting the belly open in 29th day with anesthesia. We made observation of gastric mucosas microcirculation including capillary caliber, quantity, blood flow state and microthromhosis of rats in constant temperature with image processing system. Serum contents of 6- keto-PGF1αand TXB2 were tested by radioimmunoassay method. Evaluation of index and degree of gastric mucosas injury were made by Guth standard and Whittle method. Results： Compared with sham group, degree of gastric mucosas injury was severer, meanwhile, vasodilatation, vessel wall attenuation and disorder of vessel arrangement were more obvious in AMid-aspirin group （P〈0.05）. Compared with sham group, degree of gastric mucosas injury, vasodilatation and vessel permeability were significantly severer, capillary crossing number decreased significantly in AMI＋aspirin＋clopidogrel group （P〈0.05）. Compared with sham group, gastric mucosas capillary quantity increased significantly in model group （P〈0.05）. Compared with model group, capillary caliber of gastric mucosas increased significantly in AMId. aspirin group and AMI＋aspirin＋ clopidogrel group （P〈0.01）, capillary crossing number decreaed（P（0.05） while capillary quantity increased significantly in AMI＋aspirin＋ clopidogrel group （P 〈0.01）. Compared with sham group, the content of 6-keto-PGFlo decreased significantly in model group （P〈0. 01）, the content of 6-keto-PGF1α and TXB2 decreased in different degree in AMI＋aspirin＋clopidogrel group, AMI d.aspirin group and AMI＋clopidogrel group （P〈0.05, P〈0.01）. Compare with model group, the content of 6- keto-PGF1α had no significant difference among all medicine given groups （P〉0.05） TXB2 were decreased significantly among all medicine given groups （P〈0.01）. Conclusion： Aspirin in association with clopidogrel can aggratate the gastric mucosas injury of rats with AMI. The possible mechanism is in correlated with TXB2 and 6-keto-PGF1α content inducing in blood and microcirculation disturbance of gastric mucosas.
作者
刘剑刚
张蕾
张庆翔
董国菊
史大卓
LIU Jian-gang ZHANG Lei ZHANG Qing-xiang DONG Guo-ju SHI Da-zhuo(Xiyuan Hospital of China Academy of Chinese Medical Sciences, Cardiovascular Disease Institute of Chinese Medical Sciences, Beijing 100091 Taian Traditional Chinese Medicine Hospital of Shandong Province, Taian 271000,China)
出处
《微循环学杂志》
2017年第2期1-7,共7页
Chinese Journal of Microcirculation
基金
科技部国际科技合作与交流项目(2014DFG32700
2010DFA31690)
国家自然科学基金(81273933)
关键词
急性心肌梗死
阿司匹林
氯吡格雷
胃黏膜
微循环
大鼠
Acute myocardial infarction
Aspirin
Clopidogrel
Gastric mucosas
Microcirculation
Rat
