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阿司匹林对心肌晚期缺血预适应的干预作用
Dose-dependent effects of aspirin on delay ischemic preconditioning myocardium in rabbits
【摘要】 目的:观察环氧化酶-2(COX-2)在正常心肌中表达的部位及表达量,并探索不同剂量阿司匹林作用于心肌晚期缺血预适应(DPC)后,对心肌COX-2蛋白的表达及心脏超微结构的影响。方法:采用结扎兔冠状动脉左前降支建立DPC模型。随机分为5组,分别为正常对照组,DPC组,小、中、大剂量组(阿司匹林5mg/kg、12mg/kg、20mg/kg)。实验后48h取心肌组织,应用免疫组化法、蛋白质免疫印迹法测定COX-2蛋白表达,应用电镜观察心肌超微结构的变化。结果:兔DPC组心肌COX-2蛋白表达明显高于正常对照组水平,差异有统计学意义(P<0·05);小、中剂量组对COX-2蛋白表达影响较小,差异无统计学意义(P>0·05),电镜观察心肌超微结构无明显变化;大剂量组对COX-2蛋白表达明显降低,差异有统计学意义(P<0·05),电镜证实大剂量阿司匹林对心肌超微结构的损伤加重。结论:通过缺血、缺氧可刺激心肌COX-2蛋白表达增加,大剂量阿司匹林可抑制COX-2蛋白表达,可能导致心肌损伤加重,故临床上避免在心肌DPC过程中接受大剂量阿司匹林治疗。
【Abstract】 Objective: To observe the expression of cyclooxygenase-2(COX-2) and effects of low,middle and high-dose of aspirin on delay ischemic preconditioning myocardium in rabbits.Method: A mode of ischemic preconditioning myocardium was reproduced by ligation left anterior descending branch.Thirty rabbits were randomized into five groups each consisting of six rabbits: control group, ischemic preconditiong group,low-dose group(aspirin 5 mg/kg), middle-dose group (aspirin 12 mg/kg),high-dose group(aspirin 20 mg/kg).The COX-2 protein of myocardial section was investigated by western-blotting and immunohistochemistry after 48 h, the morphologic changes of myocardial cell were investigated with electron microscope. Result:The expression of COX-2 protein in ischemic preconditioning group was significantly higher than in control group (P<0.05). The levels of COX-2 protein and the changes of myocardial cell were not different between in low dose group and middle-dose group,but the levels of COX-2 protein in high-dose group were lower than both of them (P<0.05).The injury of myocardial cell in high-dose group was most serious among them.Conclusion:The COX-2 protein is expressed in delay ischemic preconditioning myocardium in rabbits.Compared with the low and middle-dose of Aspirin,the COX-2 protein is inhabited by high-dose aspirin on prostaglandin metabolites on 24h after experiment in rabbits.It is probable that high-dose aspirin injuries the heart heavily in delay ischemic preconditioning myocardium,so we should urge caution in the administration of high-dose Aspirin to patients in ischemic preconditioning myocardium.
- 【文献出处】 临床心血管病杂志 ,Journal of Clinical Cardiology , 编辑部邮箱 ,2005年11期
- 【分类号】R541
- 【被引频次】3
- 【下载频次】126