双联抗血小板药物对大鼠胃黏膜损伤的机制  

Gastric mucosal injury induced by dual antiplatelet drugs in rats

作　　者：季英兰[1] 陆伟[2] 张志广[1] 李熳[1] 张雪莲[1] 刘霞[1] 

机构地区：[1]天津医科大学第二医院消化科,天津市300211 [2]天津市第二人民医院,天津市300192

出　　处：《世界华人消化杂志》2014年第17期2414-2420,共7页World Chinese Journal of Digestology

基　　金：天津市卫生局科技基金资助项目;No.07KG8~~

摘　　要：目的:探讨双联抗血小板药物对大鼠胃黏膜损伤及其可能发生机制.方法:SPF级♂6-7周龄SD大鼠80只,体质量200-220 g,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10.41 mg/(kg·d)、氯吡格雷7.81 mg/(kg·d)、阿司匹林联合氯吡格雷灌胃1次/d,共14 d.所有大鼠于末次给药后手术,观察胃的损伤情况,HE染色法评估胃黏膜损伤程度,免疫组织化学法测定肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-1β(interleukin-1β,IL-1β)表达水平的变化.结果:(1)各实验组大鼠胃黏膜的大体和病理损伤均高于阴性对照组(0.0000±0.00000)(P<0.01),且阿司匹林组(13.4000±3.28634)损伤高于氯吡格雷组(8.8000±1.48324)(P<0.01),双抗组(23.6000±3.57771)损伤高于阿司匹林组及氯吡格雷组(P<0.01);(2)免疫组织化学显示:与对照组(10%)相比,各实验组大鼠胃黏膜TNF-α蛋白均呈明显高水平表达(P<0.01);阿司匹林组(90%)表达水平高于氯吡格雷组(85%)(P<0.01),双抗组(100%)高于阿司匹林组及氯吡格雷组(P<0.01).与对照组(5%)相比,各实验组大鼠胃黏膜IL-1β蛋白均呈明显高水平表达(P<0.01);阿司匹林组(100%)表达水平高于氯吡格雷组(80%)(P<0.01),双抗组高于氯吡格雷组(P<0.01).结论:常规剂量抗血小板药物的使用可造成大鼠胃黏膜损伤,联合用药较单一用药造成损伤程度加重,TNF-α、IL-1β表达增强,提示这种变化可能参与黏膜的损伤.AIM： To investigate the effect of different anti- platelet drugs on gastric mucosal injury in rats and the possible mechanisms involved. METHODS： Eighty 6-7-week-old male SD rats were randomly allocated into four groups. Ex- cept a negative control group, the other three groups were given clopidogrel [7.81 mg/（kg· d）, n = 20], aspirin [10.41 mg/（kg· d）, n = 20] and clopidogrel plus aspirin （n = 20）, respectively. The drugs were intragastrically administered once daily, and the negative control group was given normal saline （n =20）. All rats received operation after the final intragastric adminis- tration to observe gastric injury. The degree of gastric and small intestinal mucosal injury wasassessed by HE staining, and the expression of tumor necrosis factor-α （TNF-α） and interleukin- 1β （IL-1β） in gastric mucosal cells was detected by immunohistochemistry. RESULTS： The scores of gross and pathological lesions were significantly higher in each drug treatment group than in the negative control group （P 〈 0.01）, in the aspirin group than in the clopidogrel group （13.4000 ± 3.28634 vs 8.8000 ±1.48324, P 〈 0.01）, and in the combination group than in the two monotherapy groups （P 〈 0.01）. Immunohistochemistry analysis revealed that the expression of TNF-α and IL-1β in the gastric and small intestinal mucosa was significantly higher in each drug treatment group than in the negative control group （P 〈 0.01）, in the aspirin group than in the clopidogrel group （P 〈 0.01）, and in the combination group than in the two monotherapy groups （P 〈 0.01）. CONCLUSION： Routine doses of antiplatelet drugs can cause gastrointestinal injury in rats, and the combination of antiplatelet drugs aggravates the injury compared with monotherapy. The high expression of TNF-α and IL-1β may be involved in mucosal injury induced by antiplatelet drugs.

关 键 词：抗血小板药物 阿司匹林 氯吡格雷 胃黏 膜损伤 

分 类 号：R965[医药卫生—药理学]