肾上腺髓质素对大鼠损伤性心肌肌浆网功能的改善

通过观察下述五个指标,评价肾上腺髓质素(adrenomedullin,Adm)对大鼠损伤性心肌肌浆网功能的改善程度左心室压力最大变化速率(±dp/dtmax)、肌浆网钙摄取和释放及钙泵活性.皮下注射异丙肾上腺素(isoproterenol,ISO,69μmol/kg体重)制备大鼠心肌损伤坏死模型.摘取心脏后用Adm灌流,观察左心室压力最大变化速率(±dp/dtmax);制备并提纯心肌肌浆网(sarcoplasmicreticulum,SR)膜,测定SRCa2+摄取和释放速率、SR钙泵活性和钙通道蛋白～3H-ryanodine受体的最大结合量.结果发现,5×10-5mol/LAdm灌流能使ISO损伤的大鼠心脏左室±dp/dtmax分别增加16.9%(2?135±281vs1?980±302)和29.2%(1?375±267vs1?064±355,均P<0.05);SRCa2+摄取和释放率分别增加23.0%(15.0±1.4vs12.2±1.2)和43.5%(6.6±1.0vs4.6±0.6,均P<0.01);SRCa2+-ATPase活性和～3H-ryanodine受体最大结合量(Bmax)分别增加24.2%(P<0.01)和42.2%(P<0.05).提示Adm对ISO诱导的大鼠心肌损伤具有保护作用,其机制可能与Adm增加SRCa2+-ATPase活性、增加～3H-ryanodine所致SRCa2+摄取和释放升高有关.外源性给予Adm对损伤心肌可能具有临床治疗作用.

Ameliorative effects of adrenomedullin on rat cardiac sarcoplasmic reticulum injured by isoproterenol

Five indices were used to assess the degree of the ameliorative effects of adrenomedullin (Adm) in isoproterenol (ISO) induced injury of cardiac sarcoplasmic reticulum (SR) of rats: +/- LV dp/dtmax, SR Ca2+ uptake, Ca2+ release (in nmol/mg SR protein) and Ca(2+)-ATPase activity. Adm (5 x 10(-5) mol/L) was perfused into rat heart before cardiac function +/- LV dp/dtmax was determined. Cardiac SR was purified and SR Ca2+ uptake, Ca2+ release, Ca(2+)-ATPase activity, and 3H-ryanodine maximal binding (Bmax) were measured. After perfusion of Adm (5 x 10(-5) mol/L), the +LV dp/dtmax and -LV dp/dtmax in ISO injured heart were increased by 16.9% (2,135 +/- 281 vs 1980 +/- 302, P < 0.05) and 29.2% (1375 +/- 267 vs 1064 +/- 355, P < 0.05), respectively. Cardiac SR Ca2+ uptake and Ca2+ release were increased by 23.0% (15.0 +/- 1.4 vs 12.2 +/- 1.2, P < 0.01) and 43.5% (6.6 +/- 1.0 vs 4.6 +/- 0.6, P < 0.01), respectively. Ca(2+)-ATPase activity and 3H-ryanodine binding were increased by 23.0% (P < 0.01) and 42.2% (P < 0.05), respectively. It seems that Adm exerted a protective effect on cardiac function in injured rat heart by enhancing SR Ca2+ uptake and release, suggesting that Adm may play a therapeutic role in myocardial injury.