Suzuki Motohisa, Suzuki Mayumi, Kitamura Yukika, Mori Saori, Sato Kazunori, Dohi Sekiko, Sato Takashi, Matsuura Akihiro, Hiraide Atsushi
Shimizu Research Laboratories, Shimizu Pharmaceutical Co, Ltd, Shizuoka, Japan.
Jpn J Pharmacol. 2002 May;89(1):36-43. doi: 10.1254/jjp.89.36.
In our previous study, beta-hydroxybutyrate (BHB) was found to prolong survival time and to inhibit cerebral edema by improving energy metabolism in the hypoxia, anoxia and global cerebral ischemia models. In this study, the cerebroprotective effect of BHB was examined in rats with permanent (p)-occlusion and transient (t)-occlusion of middle cerebral artery (MCA). BHB (30 mg x kg(-1) x h(-1) was continuously administered through the femoral vein. In rats with p-MCA occlusion, BHB significantly reduced infarct area at 24 h after the occlusion, but not at 72 h after the occlusion. In rats with 2-h t-MCA occlusion followed by 22-h reperfusion, BHB significantly reduced cerebral infarct area, edema formation, lipid peroxidation and neurological deficits. Moreover, in the t-MCA occlusion model, delayed administration of BHB started at 1 h after the initiation of the MCA occlusion also significantly reduced cerebral infarct area. Taking together the results obtained in our previous study into account, these results indicate that BHB decreased cerebral edema formation and infarct area by improving of the cerebral energy metabolism during ischemia and by inhibition of lipid peroxidation after reperfusion.
在我们之前的研究中，发现β-羟基丁酸（BHB）在缺氧、无氧和全脑缺血模型中可通过改善能量代谢来延长生存时间并抑制脑水肿。在本研究中，在大脑中动脉（MCA）永久性（p）闭塞和短暂性（t）闭塞的大鼠中检测了BHB的脑保护作用。通过股静脉持续给予BHB（30mg·kg⁻¹·h⁻¹）。在p-MCA闭塞的大鼠中, BHB在闭塞后24小时显著减小梗死面积，但在闭塞后72小时无此作用。在t-MCA闭塞2小时后再灌注22小时的大鼠中，BHB显著减小脑梗死面积、减轻水肿形成、降低脂质过氧化并改善神经功能缺损。此外，在t-MCA闭塞模型中，在MCA闭塞开始后1小时开始延迟给予BHB也显著减小脑梗死面积。综合考虑我们之前研究获得的结果，这些结果表明BHB通过在缺血期间改善脑能量代谢以及在再灌注后抑制脂质过氧化来减少脑水肿形成和梗死面积。
