Pavlovic M, Wróblewski K, Manevich Y, Kim S, Biaglow J E
University of Pennsylvania School of Medicine, Department of Radiation Oncology, Philadelphia 19104, USA.
Br J Cancer Suppl. 1996 Jul;27:S222-5.
In the present study we demonstrate that the glycolysis of the tumour 9L glioma, in vivo, may be manipulated with ketamine/xylazine combinations of anaesthetics. Xylazine alone or in combination with ketamine causes hyperglycaemia which is enhanced by glucose injections. Intracellular tumour pH is acidified when glucose is administered with ketamine/xylazine. However, the combination of inorganic phosphate and insulin with ketamine/xylazine and glucose caused an alkaline shift in the tumour pH as measured by 31P NMR. The anaesthetic combination of ketamine/acepromazine did not produce alterations in blood glucose or in tumour pH status as detected by 31P NMR spectroscopy. These results demonstrate dramatic effects of ketamine/xylazine on the acidification or alkalinisation of the cells of 9L glioma. These altered metabolic states are of potential therapeutic importance. The choice of xylazine alone would be useful for chemotherapy and hyperthermia modalities, both known to be dependent upon glucose metabolism and resultant acidification.
在本研究中,我们证明,在体内,肿瘤9L胶质瘤的糖酵解可通过氯胺酮/赛拉嗪联合麻醉剂进行调控。单独使用赛拉嗪或与氯胺酮联合使用会导致高血糖,葡萄糖注射会增强这种高血糖现象。当葡萄糖与氯胺酮/赛拉嗪一起给药时,肿瘤细胞内pH值会酸化。然而,无机磷酸盐和胰岛素与氯胺酮/赛拉嗪及葡萄糖联合使用时,通过31P核磁共振测量发现肿瘤pH值发生了碱性偏移。氯胺酮/乙酰丙嗪麻醉组合未导致血糖或通过31P核磁共振光谱检测到的肿瘤pH状态发生改变。这些结果表明氯胺酮/赛拉嗪对9L胶质瘤细胞的酸化或碱化具有显著影响。这些改变的代谢状态具有潜在的治疗重要性。单独选择赛拉嗪对化疗和热疗方式有用,这两种治疗方式都已知依赖于葡萄糖代谢及由此产生的酸化。