Effects of acute caffeine administration on NOS and Bax/Bcl2 expression in the myocardium of rat
Effects of acute caffeine administration on NOS and Bax/Bcl2 expression in the myocardium of rat
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DOI：
10.1016/j.phrs.2007.07.007
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发表时间：
2008-01-01
影响因子：
9.3
通讯作者：
Bianchi, Rossella
中科院分区：
文献类型：
--
作者：
Corsetti, Giovanni;Pasini, Evasio;Bianchi, Rossella
咖啡因是世界上最常摄入的神经活性药物，它主要用于延缓疲劳和改善体力活动。咖啡因可以调节细胞中NO的合成，并可能通过改变细胞周期而影响肌肉功能。关于心脏中咖啡因、NOS表达和细胞凋亡之间关系的数据很少，也没有关于高剂量咖啡因对体内心肌的急性影响的数据。因此，我们研究了血流动力学NOS和Bax/Bcl 2的表达在大鼠心肌后，一个单一的咖啡因管理。将32只雄性大鼠分为6组：第1组静脉注射咖啡因（16 mg/kg），第2组静脉注射咖啡因+L-NAME（30 mg/kg），第3组静脉注射咖啡因+L-arg（0.5 g/kg），第4组静脉注射咖啡因+L-NAME+L-arg，第5组静脉注射生理盐水。监测平均动脉血压（MAP）30 min后处死动物。第6组注射咖啡因，2 h后处死。分离心脏并通过免疫组织化学进行处理。我们发现咖啡因暂时增加MAP，而咖啡因+L-NAME增加MAP的时间更长。在对照心肌中，所有NOS亚型均表达。Bcl-2在核周细胞质中表达较强，而Bax在外周细胞质中表达较弱。在咖啡因和咖啡因+ L-NAME治疗的动物中，NOS表达消失。Bax和Bcl 2表达无变化。L-arg给药逆转了咖啡因和L-NAME对NOS表达的影响。咖啡因后2 h，NOS表达增加，Bax和Bcl 2表达无变化，但Bcl 2主要表达于外周细胞质。我们的结论是，改善咖啡因诱导的物理性能也可能与咖啡因的能力，干扰内源性心肌NO的合成。此外，我们认为心肌细胞对急性咖啡因给药具有有效的抗凋亡作用。(C)2007年由Elsevier Ltd.出版
Caffeine is the most frequently ingested neuroactive drug in the world and it is largely used to delay fatigue and improve physical activity. Caffeine can modulate NO synthesis in cells and may influence muscular function by modifying the cellular cycle life-death. There is little data concerning the relationship between caffeine in the heart, NOS expression and apoptosis and no data regarding the acute effect of high doses of caffeine in the in vivo myocardium. We therefore studied hemodynamic NOS and Bax/Bcl2 expression in the rat myocardium after a single cafffeine administration. Thirty-two male rats were divided into six groups: the first was iv-injected with caffeine (16 mg/kg), the second with caffeine+L-NAME (30 mg/kg), the third with caffeine+L-arg (0.5 g/kg), the fourth with caffeine+L-NAME+L-arg and finally the fifth with saline. Mean arterial blood pressure (MAP) was monitored for 30 min, then the animals were killed. The sixth group was injected with caffeine and killed after 2 h. The hearts were isolated and processed by immunohistochemistry. We found that caffeine increased MAP temporarily while caffeine +L-NAME increased it for a longer period. In the control myocardium, all NOS isoforms were expressed. The Bcl2 were strongly expressed inside the perinuclear cytoplasm whereas Bax was very faintly detectable in the peripheral cytoplasm. In caffeine and caffeine + L-NAME treated animals, NOS expression disappeared. Bax and Bcl2 expression did not vary. The L-arg administration reversed these caffeine and L-NAME effects on NOS expression. Two hours after caffeine, NOS expression increased and Bax and Bcl2 expression did not vary, although Bcl2 was mainly expressed in the peripheral cytoplasm. We conclude that improved caffeine-induced physical performance could also be related to caffeine's ability to interfere with endogenous myocardial NO synthesis. Furthermore, we suggest that myocardial cell plays an effective anti-apoptotic role against acute caffeine administration. (C) 2007 Published by Elsevier Ltd.