Gueldry S, Marie C, Rochette L, Bralet J
Laboratoire de Pharmacodynamie et Physiologie Pharmaceutique, Faculté de Pharmacie, Dijon, France.
Stroke. 1990 Oct;21(10):1458-63. doi: 10.1161/01.str.21.10.1458.
We assessed the effect of 1,3-butanediol on cerebral energy metabolism and edema after inducing multifocal brain infarcts in 108 rats by the intracarotid injection of 50-microns carbonized microspheres. An ethanol dimer that induces systemic ketosis, 25 mmol/kg i.p. butanediol was injected every 3 hours to produce a sustained increase in the plasma level of beta-hydroxybutyrate. Treatment significantly attenuated ischemia-induced metabolic changes by increasing the concentrations of phosphocreatine, adenosine triphosphate, and glycogen and by reducing the concentrations of pyruvate and lactate. Lactate concentration 2, 6, and 12 hours after embolization decreased by 13%, 44%, and 46%, respectively. Brain water content increased from 78.63% in six unembolized rats to 80.93% in 12 saline-treated and 79.57% in seven butanediol-treated rats 12 hours after embolization. (p less than 0.05). The decrease in water content was associated with significant decreases in the concentrations of sodium and chloride. The antiedema effect of butanediol could not be explained by an osmotic mechanism since equimolar doses of urea or ethanol were ineffective. Our results support the hypothesis that the beneficial effect of butanediol is mediated through cerebral utilization of ketone bodies arising from butanediol metabolism, reducing the rate of glycolysis and the deleterious accumulation of lactic acid during ischemia.
我们通过颈内注射50微米碳化微球，在108只大鼠中诱导多灶性脑梗死，评估了1,3 - 丁二醇对脑能量代谢和水肿的影响。一种能诱导全身酮症的乙醇二聚体，即每3小时腹腔注射25 mmol/kg丁二醇，以持续提高β-羟基丁酸的血浆水平。治疗通过提高磷酸肌酸、三磷酸腺苷和糖原的浓度，并降低丙酮酸和乳酸的浓度，显著减轻了缺血诱导的代谢变化。栓塞后2小时、6小时和12小时的乳酸浓度分别下降了13%、44%和46%。栓塞12小时后，脑含水量从未栓塞的6只大鼠中的78.63%，增加到生理盐水处理的12只大鼠中的80.93%，以及丁二醇处理的7只大鼠中的79.57%。（p < 0.05）。含水量的降低与钠和氯浓度的显著降低相关。丁二醇的抗水肿作用不能用渗透机制来解释，因为等摩尔剂量的尿素或乙醇无效。我们的结果支持这样的假设，即丁二醇的有益作用是通过大脑利用丁二醇代谢产生的酮体介导的，从而降低缺血期间糖酵解的速率和乳酸的有害积累。
