心房颤动犬能量代谢变化及曲美他嗪干预研究

目的 研究慢性心房颤动(房颤)犬心房能量代谢的变化,探讨曲美他嗪对房颤能量代谢和内皮功能的影响.方法 18只健康杂种犬,随机分为窦性心律组、心房起搏组和曲美他嗪组,每组6只犬.心房起搏组以400次/min快速起搏心房6周,建立房颤犬动物模型;曲美他嗪组给予曲美他嗪5 mg·kg-1·d-1口服,随后以400次/min快速起搏心房6周.采用高效液相色谱测定心肌组织磷酸肌酸(CrP)、三磷酸腺苷(ATP)、二磷酸腺苷(ADP)和一磷酸腺苷(AMP)含量,计算总腺苷酸池(TAN);用Western blot定量、免疫组化定性检测左房内皮型一氧化氮合酶(eNOS)蛋白表达,酶联免疫吸附定量检测血浆血管性血友病因子(vWF)含量,采用硝酸还原酶法测定血浆NO2-/NO3-(NOx)含量.结果 与窦性心律组相比,心房起搏6周后,心房肌CrP(P<0.01)和CrP/ATP(P<0.05)显著降低,而ATP、ADP、AMP和TAN无明显变化(P>0.05),内皮细胞功能标志物血浆vWF明显增高,NOx降低,心房eNOS蛋白表达减少.曲美他嗪治疗6周,心房肌CrP、CrP/ATP、ATP、ADP、AMP和TAN差异均无统计学意义,但eNOS蛋白表达上调(P<0.05),血浆vWF含量降低(P<0.01),NOx增加(P<0.05),内皮细胞功能改善.结论 房颤早期可出现能量代谢失衡,但随着持续时间延长,能量供求能重新达到平衡.曲美他嗪对房颤能量代谢无明显影响,但能通过一氧化氮途径改善内皮细胞功能.

Effects of chronic trimetazidine treatment on atrial energy metabolism in a canine model of chronic atrial fibrillation

Objective Aim of the present study was to investigate the effect of ehronic trimetazidine treatment on atrial energy metabolism and endothelial function in a canine model of chronic atrial fibrillation (AF).Methods Eiighteen canines were randomly divided into sham.operated group(n=6),atrial pacing group(n=6),and trimetazidine group(n=6).In atrial pacing group and trimetazidine group,dogs were atrial paced at 400 beats per minutes for 6 weeks.Trimetazidine at 5mg·kg-1·d-1 was given one day before rapid atrial pacing for 6 weeks.Creatine phosphate (CrP),adenosine triphosphate(ATP).adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in atrial tissue were analyzed by high-performance liquid chromatography.Total adenosine(TAN)Was calculated.The expression of endothetial nitric oxide synthase(eNOS)in atrial tissue was determined by Western blot and immunohistochemical staining.In addition,plasma levels of von WiUebrand factor(vWF) was quantified with enzyme-linked immunoadsorbent assay and NO2-/NO3-(NOx) was determined by nitrate reductase method.Results Atrial CrP(P<0.01) and CrP/ATP were significantly decreased in paced atrium compared to atrium from sham-operated group(P<0.05) while ATP,ADP,AMP and TAN remained unchanged (all P>0.05).Plasma vWF Was significantly increased and plasma NOx significantly decreased in paced animals compared to sham-operated animals.Atrial expression of eNOS Was also significantly reduced in paced animals(P