低血糖症中癫痫发作和昏迷的机制。胰岛素对脑内电解质转运有直接作用的证据。
Mechanisms of seizures and coma in hypoglycemia. Evidence for a direct effect of insulin on electrolyte transport in brain.
作者信息
Arieff A I, Doerner T, Zelig H, Massry S G
出版信息
J Clin Invest. 1974 Sep;54(3):654-63. doi: 10.1172/JCI107803.
The mechanisms involved in the production of hypoglycemic coma were studied in rabbits. Measurements were made in brain, cerebrospinal fluid (CSF), and plasma of osmolality, Na(+), K(+), Cl(-), water content, exogenous insulin, glucose, lactate, and glutamate, while pH, Pco(2), Po(2), and bicarbonate were evaluated in arterial blood, 35 min after i.v. injection of insulin (50 U/kg), plasma glucose did not change, but brain K(+) content increased significantly. Grand mal seizures were observed in unanesthetized animals (+/-SD) 133+/-37 min after administration of insulin, at a time when brain glucose was normal, but brain tissue content of Na(+), K(+), osmoles, and water was significantly greater than normal. Coma supervened 212+/-54 min after insulin injection, at which time brain glucose, lactate, and glutamate were significantly decreased. At both 35 and 146 min after insulin administration, exogenous insulin was present in brain, but not in the CSF. After 208 min of insulin administration, animals were given i.v. glucose and sacrificed 35 min later. Most changes in the brain produced by hypoglycemia were reversed by the administration of glucose. Hypoxia (Po(2) = 23 mm Hg) was produced and maintained for 35 min in another group of animals. Hypoxia caused brain edema but did not affect brain electrolyte content. However, brain lactate concentration was significantly greater than normal. The data indicate that the seizures noted early in the course of insulin-induced hypoglycemia are temporally related to a rise in brain osmolality secondary to an increased net transport into brain of Na(+) and K(+), probably caused by insulin, per se. As hypoglycemia persists, there is also depletion of energy-supplying substrates (glucose, lactate, glutamate) in the brain, an event which coincides with the onset of coma. The brain edema observed during hypoxia is largely due to an increase in brain osmolality secondary to accumulation of lactate.
在兔子身上研究了低血糖昏迷产生的机制。对大脑、脑脊液（CSF）和血浆中的渗透压、Na⁺、K⁺、Cl⁻、含水量、外源性胰岛素、葡萄糖、乳酸和谷氨酸进行了测量，同时在静脉注射胰岛素（50 U/kg）35分钟后，对动脉血中的pH、Pco₂、Po₂和碳酸氢盐进行了评估，血浆葡萄糖没有变化，但大脑K⁺含量显著增加。在未麻醉的动物中，注射胰岛素后133±37分钟观察到全身强直阵挛性发作，此时大脑葡萄糖正常，但大脑组织中Na⁺、K⁺、渗透压和水的含量显著高于正常水平。胰岛素注射后212±54分钟出现昏迷，此时大脑葡萄糖、乳酸和谷氨酸显著降低。在胰岛素给药后35分钟和146分钟时，大脑中存在外源性胰岛素，但脑脊液中没有。胰岛素给药208分钟后，给动物静脉注射葡萄糖，并在35分钟后处死。低血糖引起的大脑中的大多数变化通过给予葡萄糖得以逆转。在另一组动物中产生并维持缺氧（Po₂ = 23 mmHg）35分钟。缺氧导致脑水肿，但不影响大脑电解质含量。然而，大脑乳酸浓度显著高于正常水平。数据表明，胰岛素诱导的低血糖过程早期出现的癫痫发作在时间上与大脑渗透压升高有关，这是由于Na⁺和K⁺向大脑的净转运增加所致，可能是由胰岛素本身引起的。随着低血糖持续，大脑中提供能量的底物（葡萄糖、乳酸、谷氨酸）也会耗尽，这一事件与昏迷的开始同时发生。缺氧期间观察到的脑水肿主要是由于乳酸积累导致大脑渗透压升高。
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