School of Optometry and Vision Science, University of New South Wales, Sydney, Australia;
Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand;
Am J Physiol Cell Physiol. 2015 May 1;308(9):C737-49. doi: 10.1152/ajpcell.00291.2014. Epub 2015 Feb 18.
Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues.
长春西汀通过多种作用机制保护中枢神经系统免受多种退行性疾病和损伤。然而,人们对其代谢作用知之甚少。这可能非常重要,因为长春西汀对缺血有高度保护作用,缺血会抑制正常的代谢功能。本研究以缺血性视网膜为模型,研究长春西汀对代谢的影响。长春西汀降低了体外缺氧和缺血后视网膜的代谢需求,使其基于乳酸脱氢酶活性恢复到正常水平。长春西汀在视网膜缺血再灌注的体内模型中也产生了类似的效果,可能是通过增加葡萄糖的可用性。长春西汀对葡萄糖的作用似乎也改善了缺血性 Muller 细胞中的谷氨酸稳态。缺血再灌注后长春西汀的其他作用,如减少细胞死亡和改善视网膜功能,可能是药物对代谢和其他视网膜途径作用的综合结果。长春西汀的代谢作用似乎与其在缺血中的其他已知作用无关,因为它在另一个代谢模型中恢复了视网膜功能,在该模型中,Muller 细胞中的谷氨酸-谷氨酰胺代谢途径被抑制。这项研究的结果表明,长春西汀通过改变代谢来介导缺血性损伤,作为治疗神经元组织缺血的一种潜在有益方法具有潜力。