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目的 新的 α肾上腺素受体拮抗剂乌拉地尔 (阻断 α1 受体为主 ) ,治疗高血压急症、急性心肌缺血和肺水肿有效。本研究试图阐述乌拉地尔对缺血心肌内能量代谢状态、SR钙泵活力和钙释放通道的作用 ,探讨其治疗急性心肌缺血的分子和细胞机制。方法 制备急性心肌缺血家兔模型 ,给予乌拉地尔 1.0 mg· kg- 1 · d- 1 ,3天后测定缺血和非缺血区心肌内 ATP、ADP、AMP和乳酸量 ,计算能荷 ;测定 SR Ca2 + ATP酶活力和钙释放通道 [3H]Ryanodine结合的 Bmax的与 Kd值。测定心肌细胞缺氧培养及药物干预时的 SR钙泵活力。结果 缺血和梗死区心肌内 ATP、ADP、AMP含量比非缺血区下降 31%、40 %和 33% ,乳酸含量急剧升高 6 5 % ,差异显著 (P<0 .0 5和 0 .0 1) ;SR Ca2 + ATP酶活力从 (1.19± 0 .11) μmol/ g降至 0 .94μm ol/ g(P<0 .0 5 ) ;钙释放通道数目下降 ,亲和力不变。治疗组缺血心肌内 ATP、ADP、AMP含量明显回升、能荷升高 ,SR Ca2 + ATP酶活力及释放通道数目均恢复正常 (P<0 .0 5和 0 .0 1)。缺氧培养乳鼠心肌细胞钙泵活力下降 5 3% ,乌拉地尔和拉西地平药物干预时钙泵活力无明显变化。结论 乌拉地尔通过 α受体改善缺血心肌内能量代谢、减少乳酸堆积、调节 SR Ca2 +泵和钙释放通道功能、减轻钙超载是治
Purpose A new α-adrenoceptor antagonist, urapidil, which blocks α1 -receptor predominance, is effective in the treatment of acute and essential hypertension, acute myocardial ischemia, and pulmonary edema. This study attempts to elucidate the effects of urapidil on the energy metabolism state, SR calcium pump activity and calcium release channels in ischemic myocardium and to explore its molecular and cellular mechanisms for the treatment of acute myocardial ischemia. Methods A rabbit model of acute myocardial ischemia was prepared, and 1.0 mg · kg -1 · d -1 of urapidil was given. The amount of ATP, ADP, AMP and lactate in the ischemic and non-ischemic myocardium were measured after 3 days. The Kd values and the Bmax of SR Ca2 + ATPase activity and calcium release channel [3H] Ryanodine binding were determined. The cardiomyocyte hypoxia culture and drug intervention SR calcium pump activity. Results The levels of ATP, ADP and AMP in myocardium were decreased by 31%, 40% and 33% respectively compared with non-ischemic area, and the content of lactate increased by 65% (P <0.05). The activity of SR Ca2 + ATPase decreased from (1.19 ± 0.11) μmol / g to 0.94 μmol / g (P <0.05), while the number of calcium releasing channels decreased and the affinity remained unchanged. The content of ATP, ADP and AMP in the ischemic myocardium of the treatment group rose significantly, the energy load increased, the activity of SR Ca2 + ATPase and the number of the release channels returned to normal (P <0.05 and 0.01). The hypoxia cultured cardiomyocytes calcium pump activity decreased 53%, urapidil and lacidipine drug intervention calcium pump activity no significant change. Conclusion Urapidil can improve myocardial energy metabolism, reduce lactic acid accumulation, regulate the function of SR Ca2 + pump and calcium release channels, and reduce calcium overload through α receptor.