Suzuki M, Suzuki M, Sato K, Dohi S, Sato T, Matsuura A, Hiraide A
Shimizu Research Center, Research and Development Division, Shimizu Pharmaceutical Co., Ltd., Shizuoka, Japan.
Jpn J Pharmacol. 2001 Oct;87(2):143-50. doi: 10.1254/jjp.87.143.
Although improving energy metabolism in ischemic brain has been accepted for the treatment of cerebrovascular diseases, administration of glucose, as an energy substrate, would aggravate ischemic brain damage via activating anaerobic glycolysis, which leads to lactate accumulation. Beta-hydroxybutyrate (BHB) is one of the ketone bodies that can be utilized as an energy source during starvation. The purpose of our study was to define the protective effects of BHB on brain damage induced by hypoxia, anoxia and ischemia. The isotonic solution of BHB administered 30 min before the induction of ischemia at doses over 50 mg x kg(-1) x h(-1) showed remarkable protective effects against hypoxia and anoxia. BHB administered immediately after a bilateral carotid artery ligation at a dose of 30 mg x kg(-1) x h(-1) significantly suppressed the elevation of cerebral water and sodium contents as well as maintaining high ATP and low lactate levels. In contrast, glycerin, a hypertonic agent, substantially reduced the water content but did not show any significant effect on other parameters. We demonstrated that BHB, unlike glycerin, when used as an energy substrate in ischemic brain, has protective effects on cerebral hypoxia, anoxia and ischemia-induced metabolic change.
尽管改善缺血性脑的能量代谢已被认可用于治疗脑血管疾病，但作为能量底物给予葡萄糖会通过激活无氧糖酵解加重缺血性脑损伤，进而导致乳酸堆积。β-羟基丁酸（BHB）是酮体之一，在饥饿期间可作为能量来源。我们研究的目的是确定BHB对缺氧、无氧和缺血诱导的脑损伤的保护作用。在缺血诱导前30分钟给予剂量超过50mg·kg⁻¹·h⁻¹的BHB等渗溶液，对缺氧和无氧显示出显著的保护作用。在双侧颈动脉结扎后立即给予剂量为30mg·kg⁻¹·h⁻¹的BHB，可显著抑制脑水和钠含量的升高，并维持高ATP水平和低乳酸水平。相比之下，高渗剂甘油可大幅降低水含量，但对其他参数无显著影响。我们证明，与甘油不同，BHB在缺血性脑中用作能量底物时，对脑缺氧、无氧和缺血诱导的代谢变化具有保护作用。
