Miller A L, Hatch J P, Prihoda T J
Department of Psychiatry, University of Texas Health Science Center, San Antonio 78284-7792.
Metab Brain Dis. 1990 Dec;5(4):195-204. doi: 10.1007/BF00997073.
Dichloroacetate (DCA) activates pyruvate dehydrogenase (PDH) by inhibiting PDH kinase. Neutralized DCA (100 mg/kg) or saline was intravenously administered to 20 to 25-day-old rats (50-75g). Fifteen minutes later a mixture of [6-14C]glucose and [3H]fluorodeoxyglucose (FDG) was administered intravenously and the animals were sacrificed by microwave irradiation (2450 MHz, 8.0 kW, 0.6-0.8 sec) after 2 or 5 min. Brain regional rates of glucose use and metabolite levels were determined. DCA-treated rats had increased rates of glucose use in all regions studied (cortex, thalamus, striatum, and brain stem), with an average increase of 41%. Lactate levels were lower in all regions, by an average of 35%. There were no significant changes in levels of ATP, creatine phosphate, or glycogen in any brain region. Blood levels of lactate did not differ significantly between the DCA- and the saline-treated groups. Blood glucose levels were higher in the DCA group. In rats sacrificed by freeze-blowing, DCA treatment caused lower brain levels of both lactate and pyruvate. These results cannot be explained by any systemic effect of DCA. Rather, it appears that in the immature rat, DCA treatment results in activation of brain PDH, increased metabolism of brain pyruvate and lactate, and a resulting increase in brain glycolytic rate.
二氯乙酸（DCA）通过抑制丙酮酸脱氢酶激酶来激活丙酮酸脱氢酶（PDH）。将中和后的DCA（100毫克/千克）或生理盐水静脉注射给20至25日龄的大鼠（50 - 75克）。15分钟后，静脉注射[6 - 14C]葡萄糖和[3H]氟脱氧葡萄糖（FDG）的混合物，2或5分钟后通过微波辐射（2450兆赫，8.0千瓦，0.6 - 0.8秒）处死动物。测定脑区葡萄糖利用速率和代谢物水平。接受DCA治疗的大鼠在所有研究区域（皮层、丘脑、纹状体和脑干）的葡萄糖利用速率均增加，平均增加41%。所有区域的乳酸水平均降低，平均降低35%。任何脑区的ATP、磷酸肌酸或糖原水平均无显著变化。DCA治疗组和生理盐水治疗组的血液乳酸水平无显著差异。DCA组的血糖水平较高。在通过冷冻吹气处死的大鼠中，DCA治疗导致脑内乳酸和丙酮酸水平降低。这些结果无法用DCA的任何全身效应来解释。相反，在未成熟大鼠中，DCA治疗似乎导致脑PDH激活、脑丙酮酸和乳酸代谢增加，从而使脑糖酵解速率增加。
