Apelin-13对离体大鼠心脏缺血/再灌注损伤的影响及机制探讨  

Effects and mechanisms of apelin-13 on ischemia/reperfusion injury in rat heart

作　　者：曾翔俊[1] 王红霞[1] 芦玲巧[1] 郝刚[1] 王晓燕[1] 马利权[1] 邱笑违[1] 张立克[1] 唐朝枢[2] 

机构地区：[1]首都医科大学病理生理学教研室,北京100069 [2]北京大学第一医院心血管研究所,北京100034

出　　处：《中国药理学通报》2007年第1期82-85,共4页Chinese Pharmacological Bulletin

基　　金：北京市自然科学基金资助项目(No7062007);北京市教委基金资助项目(NoKM200510025009)

摘　　要：目的观察apelin-13对离体大鼠缺血/再灌注损伤的影响,并初步探讨其作用机制。方法Langendorff恒流灌注大鼠心脏,采用停灌/复灌方式复制缺血/再灌注模型;观察缺血/再灌注期间心脏收缩期左心室内压上升的最大变化速率(+LVdp/dtmax)及舒张期左心室内压下降的最大变化速率(-LVdp/dtmax);采用比色法检测乳酸脱氢酶(LDH)及超氧化物歧化酶(SOD)活性的变化,Westernblot方法检测内皮型一氧化氮合酶(eNOS)和ERK1/2的表达。结果apelin-13可以增加缺血/再灌注损伤后心脏±dp/dtmax(P<0·01),降低灌流液中LDH水平,增加心肌组织中SOD活性,上调心肌组织中eNOS表达和下调细胞外调节蛋白激酶1和2(ERK1/2)的表达。结论apelin-13拮抗缺血/再灌注引起的心脏收缩及舒张功能障碍及心肌细胞膜稳定性改变;其作用机制可能与增加心肌清除氧自由基的能力、改变eNOS与ERK1/2表达有关。Aim To observe effects and mechanisms of apelin-13 on ischemia/reperfusion injury in rat heart in virtro. Methods The ischemia/reperfusion models of rat heart in vitro were made through stopping and reperfusion of the KH fluid to the heart; observing changes of maximal rate of the pressure increase （ ＋ dp/dtmax） and maximal rate of the pressure decrease （-dp/dtmax） of heart. Colorimetric method was used to assay the content of lactate dehydrogenase （LDH） and activity of superoxide dismutase （SOD）. Western blot was used to assay endothelial NO synthase （eNOS） and extracellular-regulated kinases （ ERK1/ 2）. Results Groups given low-dosage （30 pmol · L^-1） and high dosage （100 pmol · L^-1） apelin-13 had higher ±LVdp/dtmax （ P 〈 0. 01 ） ; and the leakage of myocardial LDH were attenuated in the group given low-dosage （30 pmol · L^-1 ） apelin-13 ; administration of apelin-13 before and after ischemia/reperfusion resuited in hyper-expression of SOD and eNOS （P 〈 0. 05 ） ,while the expression of ERK1/2 were down regulated （ P 〈 0. 05 ）. Conclusion The protective effects of apelin-13 on ischemia/reperfusion injury in rat heart in vitro may involved in stabilizing the cell membrane of the myocardium, clearing more oxygen-derived free radicals and relaxing the coronary artery.

关 键 词：缺血/再灌注损伤 apelin多肽 心肌 

分 类 号：R-332[医药卫生] R322.11