双联抗血小板聚集药物致小肠损伤的动物实验研究

The Experimental Study on Dual Antiplatelet Drugs-Induced Intestinal Damage in Rats

目的探讨双联抗血小板聚集药物对大鼠小肠损伤的情况。方法 SD大鼠80只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(双抗组),每组20只,每天分别予生理盐水、阿司匹林10.41 mg/kg、氯吡格雷7.81 mg/kg、阿司匹林10.41 mg/kg联合氯吡格雷7.81 mg/kg灌胃,共14 d。所有大鼠于末次给药后手术,观察小肠损伤情况,取空肠液行细菌培养,溴化乙锭(EB)行小肠通透性检测,按照Chiu方法进行小肠黏膜病理损伤评分。结果各实验组大鼠小肠黏膜均出现不同程度损伤,病理损伤评分均高于阴性对照组,且以双抗组最高(3.450±1.356)分。与对照组[(54.012±3.513)μg/g]相比,各实验组大鼠小肠通透性均明显增高,双抗组高于阿司匹林组及氯吡格雷组(μg/g:130.533±29.631 vs 90.965±3.765 vs 66.800±4.853,P<0.001)。双抗组大鼠空肠液细菌总量较对照组明显增多(CFU/mL:61 924.805±1 751.159 vs 18 154.280±1 153.376,P<0.001),肠杆菌与肠球菌比例较对照组明显下降(0.220±0.089 vs 1.007±0.148,P<0.001)。结论常规剂量双联抗血小板聚集药物的使用较单一用药造成大鼠小肠损伤程度加重,肠道细菌数量增多,菌群失调、小肠通透性的增高都可能是小肠黏膜损伤的重要表现。

Objective To investigate the effect of dual antiplatelet drugs on the intestinal damage in rats. Meth-ods Eighty SD rats were randomly allocated into four groups：control group （normal saline, n=20）, aspirin group （10.41 mg/kg, n=20）, clopidogrel group （7.81 mg/kg, n=20） and clopidogrel combined aspirin group （n=20）. Each group was given intra-gastric administration of drugs once per day for 14 days. All rats received operation after the final intragastric administration. The intestinal injury was observed. The jejunal fluid was taken for bacterial culture. The intestinal permeability was detected by ethidium bromide （EB） method. The small intestinal mucosal injury was estimated by Chiu method. Results The differ-ent degrees of small intestinal mucosal injury were found in four groups. The scores of pathological lesions were significantly higher in aspirin group, clopidogrel group and clopidogrel combined aspirin group than those of control group （P〈0.05）. The dual antiplatelet group showed the highest score （3.450±1.356）. The small intestinal permeability was significantly increased in experiment groups compared with that of control group （54.012±3.513μg/g, P〈0.05）. There was a significantly higher small intestinal permeability in dual antiplatelet group than that of aspirin group and clopidogrel group （μg/g：130.533 ± 29.631 vs 90.965±3.765 vs 66.800±4.853, P〈0.001）. The total jejunal bacteria was significantly increased in dual antiplate-let group than that of control group （CFU/mL：61924.805±1751.159 vs 18154.280±1153.376, P〈0.001）. The ratio of entero-bacterium and enterococcus was significantly decreased in dual antiplatelet group compared with that of control group （0.220±0.089 vs 1.007±0.148, P〈0.001）. Conclusion The routine dose of dual antiplatelet drug aggravates the small intes-tinal injury in rats compared with that of single drug. The manifestations of intestinal mucosal injury include increased intes-tinal bacteria, dysbacteriosis, and increased small intestinal permeability.