果糖二磷酸钠对大鼠心肌缺血的防治作用及其机制  

Effects of fructose-1,6-diphosphate on myocardial ischemia in rats

作　　者：张清友[1] 魏冰[1] 宫丽敏[1] 齐建光[1] 张春雨[1] 杜军保[1] 汤秀英[2] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院病理科,北京100034

出　　处：《中国药理学通报》2002年第6期631-634,共4页Chinese Pharmacological Bulletin

摘　　要：目的　研究口服果糖二磷酸钠对异丙肾上腺素致大鼠心肌缺血时心肌细胞的凋亡及对心肌细胞肌浆网钙泵活性的影响。方法　在大鼠皮下注射异丙肾上腺素造成的心肌缺血坏死模型上 ,同时给予果糖二磷酸钠灌胃 ,观察心肌病理变化 ,以缺口末端标记法 (TUNEL)及免疫组化法检测心肌凋亡细胞、心肌细胞Fas、Bcl 2基因蛋白表达的变化 ,及应用 p 硝苯基磷酸法测定心肌细胞肌浆网钙泵活性变化 ,应用原子吸收法测定心肌钙含量。结果　应用异丙肾上腺素可导致明显的心肌缺血坏死及纤维化 ;缺血心肌组织中心肌细胞凋亡指数及Fas、Bcl 2基因蛋白表达量增加 (P <0 0 1) ,同时心肌细胞肌浆网钙泵活性降低 (P <0 0 5 )而心肌的钙含量却升高 (P <0 0 5 )。应用果糖二磷酸钠灌胃治疗能明显减轻心肌坏死及纤维化 (P <0 0 1) ,降低心肌组织细胞的凋亡 (P <0 0 5 )、心肌组织Fas基因的蛋白表达 (P <0 0 5 )及上调Bcl 2基因的蛋白的表达 (P <0 0 5 ) ;而且可以部分恢复心肌细胞肌浆网的钙泵活性 (P <0 0 5 ) ,降低心肌钙含量 (P <0 0 5 )。结论　口服果糖二磷酸钠可以保护由儿茶酚胺增多所引起的心肌缺血损伤 ,其机制与其能恢复心肌细胞肌浆网上的钙泵活性 ,调节心肌细胞的钙代谢紊乱 。AIM To study the effects of FDP on myocyte apoptosis and the expression of apoptosis associated genes in rat hearts with myocardial ischemia induced by isoproterenol(Iso).The effects of FDP on sarcoplasmic reticulum(SR) Ca 2+ ATPase of ischemic myocardia were also investigated. METHODS Myocyte apoptosis and the protein expression of Fas and Bcl 2 were estimated by terminal deoxynucleotide transferase(TdT) mediated dUTP nick end labeling (TUNEL) and S P immunohistochemistry respectively.The activity of myocardial Sarco/Endoplasmic Ca 2+ ATPase (SERCA) and calcium content of myocardia were also observed. RESULTS myocardial ischemia induced by Iso presented obvious myocardial necrosis and fibrosis. Compared with contral group,the apoptotic indices(AI), the positive expresion indices(PEI) of Fas and Bcl 2 proteins in myocytes increased significantly in Iso group .Meanwhile,the activity of myocardial SERCA decreased greatly. Compared with Iso group,AI and PEI of Fas protein decreased in FDP group,but the activity of myocardial SERCA increased and calcium content of myocardia deceased significantly. CONCLUSIONS FDP exerts some protective effects on myocardial ishemia induced by Iso in rats.One of mechanisms may be due to the improvement of the activity of myocardial SERCA in the mice,then downregulating the protein expression of Fas gene,thereby inhibiting myocyte apoptosis.

关 键 词：果糖二磷酸钠 异丙肾上腺素 心肌缺血损伤 肌浆网 钙泵活性 细胞凋亡 

分 类 号：R542.22[医药卫生—心血管疾病] R965[医药卫生—内科学]