地高辛抗体对大鼠再灌注心肌一氧化氮合酶同工酶表达的影响  

Effects of antidigoxin antiserum on expression of NOSs in ischemia-reperfusion myocardium of rats

作　　者：王星[1] 王德国[1] 柯永胜[1] 唐振国[1] 杨玉雯[1] 王安才[1] 

机构地区：[1]皖南医学院附属弋矶山医院老年医学科

出　　处：《中国临床药理学与治疗学》2008年第7期753-757,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省教育厅自然科学基金资助项目(2006KJ109C)

摘　　要：目的:观察心肌缺血再灌注(myocardial ischemia reperfusion,MIR)时大鼠心肌组织、血清NO水平及一氧化氮合酶(NOS)同工酶蛋白表达的变化和内洋地黄素特异性抗体对MIR时心肌NO系统损伤的保护作用。方法:采用左冠状动脉前降支结扎30min,复灌45min建立在体大鼠MIR模型,Sprauge-Dawley大鼠随机分成7组,每组10只:假手术组,MIR模型组,生理盐水组,维拉帕米组,小、中、高剂量地高辛抗血清组(9、18、36mg/kg)。各组于再灌注45min后立即取左室心尖部缺血区心肌并断尾取血,检测心肌匀浆和静脉血中NO含量,心肌匀浆中的内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)水平,免疫组织化学SABC法检测心肌组织eNOS、iNOS;光镜下观察心肌组织形态学变化。结果:MIR时心肌组织NO水平明显降低,但血清中NO水平无明显变化;eNOS表达明显减少,iNOS表达明显增加,心肌组织结构发生明显损伤;中、高剂量地高辛抗血清能有效降低心肌组织iNOS表达,恢复心肌细胞eNOS活性,提高心肌组织和血液中的NO水平,减轻MIR导致的心肌组织结构损伤。结论:内洋地黄素特异性抗体对MIR造成的心肌NO系统损伤具有明显的保护作用,其作用机制可能通过拮抗内洋地黄素,调节心肌NOS同工酶的表达紊乱而实现。AIM： To investigate the changes of myocardial NO levels and the expression of NOS isoforms in rats with myocardial ischemia reperfusion （M1R） and the protective effect of anti-digoxin antiserum, an digoxin specific antagonist, on MIR induced NO system injury. METHODS： Myocardial ischemia reperfusion injury models were made by ligating the left anterior descending coronary artery for 30 min and followed by 45 min reperfusion Sprauge-Dawley rats were randomly divided into seven groups each with 10 rats including sham group, MIR group, normal saline group, verapamil group , low dose, middle dose and high dose anti-digoxin antiserum groups. The NO levels of myocardial and serum , activities of eNOS and iNOS were measured. The expression of myocardial eNOS and iNOS were determined by i mmunohistochemisry. The myocardial morphology was observed under optical microscope. RESULTS： The myocardial NO levels were significantly increased; The serum NO levels did not changed significantly; The eNOS expression were significantly decreased; The iNOS expression were significantly increased. Meanwhile, myocardial morphology injury was remarkable. With the intervention of middle and high dose anti-digoxin antiserum, the expression of myocardial iNOS were significantly depressed, the eNOS expression were reverted, the serum and myocardium NO levels were significantly increased. The myocardial histological morphology was significantly improved. CONCLUSION： The anti-digoxin antiserum can protect the function of myocardial NO system against MIR. The mechanism maybe antag- onize endoxin and regulate the expression of NOS isoforms in myocardium.

关 键 词：内洋地黄素 缺血再灌注损伤 心肌 一氧化氮合酶 地高辛抗体 

分 类 号：R541.4[医药卫生—心血管疾病]