阿司匹林和氯吡格雷联合应用致急性心肌梗死后大鼠胃黏膜损伤和微血管变化的药理机制初探

发布时间：2019-05-14 23:56

【摘要】：目的结扎大鼠冠状动脉前降支造成大鼠实验性急性心肌梗死(AMI)模型,观察联合应用阿司匹林和氯吡格雷对AMI后大鼠胃黏膜微血管的影响,探讨双联抗致大鼠胃黏膜损伤可能的药理作用机制。方法将SD大鼠腹腔麻醉(4%水合氯醛,9 m L·kg-1体质量)后常规处理,结扎左冠状动脉前降支血管造成大鼠实验性AMI模型,确定成活的大鼠随机分为(1)模型(AMI)对照组:灌胃蒸馏水2 mg·kg-1·d-1;(2)阿司匹林组:灌胃阿司匹林9 mg·kg-1·d-1;(3)氯吡格雷组:灌胃氯吡格雷6.75 mg·kg-1·d-1;(4)双联抗组:灌胃阿司匹林9mg·kg-1·d-1和氯吡格雷6.75 mg·kg-1·d-1混悬液。另取12只大鼠作为假手术组(只穿刺不结扎冠脉,其余处理方法与AMI模型组相同),每组12只,雌雄各半,连续灌胃28 d后,第29 d进行微血管形态的观察,实验结束后腹主动脉取血,放射免疫法测定胃泌素(GAS)、胃动素(MTL)和6-酮-前列腺素F1α(6-keto-PGF1α)和血栓素B2(TXB2)指标,大鼠胃黏膜分别按照Guth标准和Whittle方法评定损伤指数和胃黏膜损伤程度。结果经Guth方法和Whittle标准的计分评定和假手术组比较,小剂量阿司匹林组大鼠胃黏膜损伤及程度明显,阿司匹林联合氯吡格雷后胃黏膜损伤程度加重,胃黏膜微血管扩张,血管壁变薄,毛细血管交叉数减少显著(P0.05),大鼠血浆GAS水平显著降低(P0.01),MTL水平显著升高(P0.01)。阿司匹林组的GAS降低水平和MTL升高水平大于氯吡格雷组,和假手术组比较,阿司匹林组可以显著降低TXB2水平。结论阿司匹林和氯吡格雷联合应用可加重AMI后大鼠胃黏膜的损伤,其机制与胃肠激素水平紊乱、干扰前列腺素合成导致胃黏膜微血管障碍密切相关。
[Abstract]:Objective to observe the effect of aspirin and clopidogrel on gastric mucosal microvessels in rats with experimental acute myocardial infarction (AMI) induced by ligating the anterior descending branch of coronary artery in rats. To explore the possible pharmacological mechanism of double anti-gastric mucosal injury in rats. Methods the experimental AMI model was established by ligating the anterior descending branch of the left coronary artery after intraabdominal anesthesia (4% chloral hydrate, 9 mL kg-1 body mass) in SD rats. The surviving rats were randomly divided into (1) model (AMI) control group: distilled water was given intragastrically 2 mg kg- 1 路d-1; (2) aspirin group: aspirin 9 mg kg- 1 路d-1, clopidogrel 6.75 mg kg- 1 路d-1; (4) double antibody group: aspirin 9mg kg- 1 路d-1 and clopidogrel 6.75 mg kg- 1 路d-1 suspension were given intragastrically. Another 12 rats were taken as false operation group (only puncture without ligating coronary artery, and the other treatments were the same as those in AMI model group). 12 rats in each group, half male and half female, were given intragastrically for 28 days, and the morphology of microvessels was observed on the 29th day. At the end of the experiment, blood was taken from abdominal aortic, and the indexes of (GAS), motilin (MTL), 6-keto-prostaglandin F1 伪 (6-keto-PGF1 伪) and thromboxane B2 (TXB2) were measured by radioimmunoassay. The injury index and degree of gastric mucosa injury were evaluated according to Guth standard and Whittle method, respectively. Results compared with the false operation group, the injury and degree of gastric mucosa in the low dose aspirin group were significantly higher than those in the false operation group by Guth method and Whittle standard score. The degree of gastric mucous membrane injury was aggravated and the microvessels of gastric mucosa were dilated after aspirin combined with clopidogrel. The blood vessel wall became thinner, the number of capillary crossing decreased significantly (P 0.05), and the plasma GAS level decreased significantly (P 0.01), MTL level). The decreased level of GAS and the increase of MTL in aspirin group were higher than those in clopidogrel group. Compared with the pseudo-operation group, aspirin group could significantly decrease the level of TXB2. Conclusion combination of aspirin and clopidogrel can aggravate the injury of gastric mucosa in rats after AMI, and its mechanism is closely related to the disorder of gastrointestinal hormone levels and the microvascular disorder of gastric mucosa caused by interference with prostaglandin synthesis.
【作者单位】：中国中医科学院西苑医院中国中医科学院心血管病研究所;山东省泰安市中医医院;
【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)
【分类号】：R542.22

【相似文献】