Animal Experimental Study On The Mechanism Of Gastrointestinal Injury By Dual Antiplatelet Drug

ObjectiveObservation of aspirin, clopidogrel, aspirin clopidogrel (dual antiplatelet drugs) on rat stomach, small intestine injury situation and to explore the relationship between the different experimental groups stomach, small intestine damage and expression of inflammatory cytokines, for the future prevention of antiplatelet drug-related gastrointestinal damage, provide an experimental basis.MethodsThe80SD rats (6-7weeks old, weighing200～220g, male outbred population Sprague Dawley) were randomly divided into negative control group, aspirin, clopidogrel, aspirin plus clopidogrel groups of20; were given daily saline, aspirin10.41mg/kg, clopidogrel7.81mg/kg,7.81mg/kg clopidogrel combined with aspirin10.41mg/kg gavage for14days. All rats in surgery after the last administration of the stomach and small intestine for gross lesion score, the stomach, small intestine tissue after HE staining histological injury scores and analysis of inflammatory cytokines TNF-a by immunohistochemistry,IL-1β expression of.Results1the rat gastrointestinal tract injury score generally results:by Guth standard gastric lesions index, Negative control group was0.000±0.000, aspirin group was3.550±0.822, clopidogrel group was2.200±0.443, aspirin plus clopidogrel group was4.550±0.915, F=57.393, P<0.05, statistically significant results. According to Reuter scoring intestinal damage index, the negative control group was0.000±0.000; aspirin group was2.950±0.710; clopidogrel group was1.600±0.595; aspirin plus clopidogrel group was3.400±0.950, F=46.566, P<0.05The results were statistically significant.2rat gastrointestinal mucosal injury score morphological results:Rat stomach, small intestine morphological injury score results:according to the degree of light endoscopic mucosal injury criteria for each group of grading gastric mucosal injury, gastric mucosal injury in the negative control group dominated O100%, aspirin damage is in class Ⅱ and class；Ⅲ～Ⅳ injuries, accounting for80%of the clopidogrel group to class Ⅰ and class Ⅱ mainly accounted for approximately80%of clopidogrel to aspirin grade Ⅱ～Ⅳ injury based,accounted for95%,P<0.05, statistically significant results.According to Chiu’s scoring criteria for small intestinal lesion scores,the control group was0.000士0.000,aspirin group was2.030±1.114, clopidogrel group was1.089±0.792,aspirin plus clopidogrel group was3.550±1.451.F=42.833,P<0.05,statistically significant resulls.3the expression of inflammatory cytokines in rat stomach and small intestine TNF-α,IL-1β:Gastric tissue TNF-α expression,negative control group to negative(一)/(±) expression,accounting for90%of the aspirin group damage to positive(++)based40%and20%the strongly positive(+++)expression,clop；dogrel weak positive (+)expression mainly accounted for approximately55%of clopidogrel to aspirin strongly positive(+++)expression mainly accounted for65%,P<0.05,statistically significant results.Gastric tissue expression of IL-1β,negative control group to negative(一)/(±)expression,accounting for95%of the aspirin group damage to positive(++)based45%and30%the strongly positive(+++)expression, clopidogrel weak positive(+)expression mainly accounted for approximately50%of clopidogrel to aspirin strongly positive(+++)expression mainly accounted for70%,P<0.05,statistically significant results.Intestinal tissue TNF-α expression in the negative control group to negative(一)/(±)expression,accounting for95%of the aspirin group damage to positive(++) mainly accounted for40%and25%the strongly positive(+++)expression, clopidogrel weak positive(+)and positive(++)expression mainly accounted for approximately85％of clopidogrel to aspirin strongly positive(+++)expression mainly accounted for60%,P<0.05,statistically significant results.Intestinal tissue IL一1β expression,negative control group to negative(一)/(±)expression,accounting for95%of the aspirin group damage to positive(++)mainly accounted for45%and30%the strongly positive(+++)expression,clopidogrel weak positive(+) expression mainly accounted for approximately50%of clopidogrel to aspirin strongly positive(+++)expression mainly accounted for70%,P<0.05,statistically significant results. Conclusion:1, antiplatelet drugs can cause gastric mucosal injury in rats, a single aspirin on gastrointestinal mucosal injury compared with clopidogrel alone a little heavy, the heaviest drug clopidogrel aspirin on gastric mucosal injury.2, antiplatelet drugs can cause small intestinal mucosal injury in rats, aspirin alone on rat small intestinal mucosal injury compared with clopidogrel alone slightly heavier, aspirin plus clopidogrel medication heaviest damage to the small intestine.3, inflammatory factor TNF-a, IL-1β are highly expressed in the antiplatelet drugs induced rat small intestinal injury in the stomach, indicating that the inflammatory response in the antiplatelet drugs cause rat stomach, small intestine damage may play an important role.