Horinaka N, Artz N, Jehle J, Takahashi S, Kennedy C, Sokoloff L
Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
J Cereb Blood Flow Metab. 1997 Jan;17(1):54-63. doi: 10.1097/00004647-199701000-00008.
Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 mM, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3- concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 mM) or pharmacological doses of deoxyglucose.
当大脑的葡萄糖供应因低血糖而受限或葡萄糖代谢被药理剂量的2-脱氧葡萄糖（DG）抑制时，脑血流量（CBF）会增加。目前在未麻醉的胰岛素诱导低血糖大鼠中的研究表明，用[14C]碘安替比林法测量的CBF增加相对较小，直到动脉血浆葡萄糖水平降至2.5至3.0 mM，此时CBF会急剧上升。排除了胰岛素对CBF的直接作用；在通过葡萄糖注射维持的正常血糖条件下给予胰岛素对CBF没有影响。胰岛素给药会提高血浆乳酸水平，降低血浆K+和HCO3-浓度以及动脉pH值。然而，这些与CBF的增加无关，因为在正常血糖条件下的胰岛素具有类似的作用但不影响CBF；此外，用药理剂量（静脉注射200 mg/kg）的DG抑制脑葡萄糖代谢会增加CBF，就像胰岛素低血糖一样，而不会改变血浆乳酸和K+水平以及动脉血气张力和pH值。一氧化氮似乎也不介导CBF的增加。通过每天两次腹腔注射NG-硝基-L-精氨酸甲酯连续4天慢性阻断一氧化氮合酶活性，或通过单次静脉注射急性阻断，会升高正常血糖、低血糖和DG处理大鼠的动脉血压并降低CBF，但不会显著降低因胰岛素诱导的低血糖（动脉血浆葡萄糖水平为2.5 - 3 mM）或药理剂量的脱氧葡萄糖导致的CBF增加。
