【摘要】：目的結(jié)扎大鼠冠狀動(dòng)脈前降支造成大鼠實(shí)驗(yàn)性急性心肌梗死(AMI)模型,觀察聯(lián)合應(yīng)用阿司匹林和氯吡格雷對(duì)AMI后大鼠胃黏膜微血管的影響,探討雙聯(lián)抗致大鼠胃黏膜損傷可能的藥理作用機(jī)制。方法將SD大鼠腹腔麻醉(4%水合氯醛,9 m L·kg-1體質(zhì)量)后常規(guī)處理,結(jié)扎左冠狀動(dòng)脈前降支血管造成大鼠實(shí)驗(yàn)性AMI模型,確定成活的大鼠隨機(jī)分為(1)模型(AMI)對(duì)照組:灌胃蒸餾水2 mg·kg-1·d-1;(2)阿司匹林組:灌胃阿司匹林9 mg·kg-1·d-1;(3)氯吡格雷組:灌胃氯吡格雷6.75 mg·kg-1·d-1;(4)雙聯(lián)抗組:灌胃阿司匹林9mg·kg-1·d-1和氯吡格雷6.75 mg·kg-1·d-1混懸液。另取12只大鼠作為假手術(shù)組(只穿刺不結(jié)扎冠脈,其余處理方法與AMI模型組相同),每組12只,雌雄各半,連續(xù)灌胃28 d后,第29 d進(jìn)行微血管形態(tài)的觀察,實(shí)驗(yàn)結(jié)束后腹主動(dòng)脈取血,放射免疫法測(cè)定胃泌素(GAS)、胃動(dòng)素(MTL)和6-酮-前列腺素F1α(6-keto-PGF1α)和血栓素B2(TXB2)指標(biāo),大鼠胃黏膜分別按照Guth標(biāo)準(zhǔn)和Whittle方法評(píng)定損傷指數(shù)和胃黏膜損傷程度。結(jié)果經(jīng)Guth方法和Whittle標(biāo)準(zhǔn)的計(jì)分評(píng)定和假手術(shù)組比較,小劑量阿司匹林組大鼠胃黏膜損傷及程度明顯,阿司匹林聯(lián)合氯吡格雷后胃黏膜損傷程度加重,胃黏膜微血管擴(kuò)張,血管壁變薄,毛細(xì)血管交叉數(shù)減少顯著(P0.05),大鼠血漿GAS水平顯著降低(P0.01),MTL水平顯著升高(P0.01)。阿司匹林組的GAS降低水平和MTL升高水平大于氯吡格雷組,和假手術(shù)組比較,阿司匹林組可以顯著降低TXB2水平。結(jié)論阿司匹林和氯吡格雷聯(lián)合應(yīng)用可加重AMI后大鼠胃黏膜的損傷,其機(jī)制與胃腸激素水平紊亂、干擾前列腺素合成導(dǎo)致胃黏膜微血管障礙密切相關(guān)。
[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 偽 (6-keto-PGF1 偽) 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.
【作者單位】： 中國(guó)中醫(yī)科學(xué)院西苑醫(yī)院中國(guó)中醫(yī)科學(xué)院心血管病研究所;山東省泰安市中醫(yī)醫(yī)院;
【基金】：科技部國(guó)際科技合作與交流項(xiàng)目(2014DFG32700,2010DFA31690) 國(guó)家自然科學(xué)基金(81273933)
【分類(lèi)號(hào)】：R542.22

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