Knudsen G M, Jakobsen J
Department of Neurology, University Clinic, Rigshospitalet, Copenhagen, Denmark.
J Neurochem. 1989 Jan;52(1):174-8. doi: 10.1111/j.1471-4159.1989.tb10913.x.
In order to explore the pathogenetic mechanism underlying the changes in blood-brain barrier sodium transport in experimental diabetes, the effects of hyperglycemia and of hypoinsulinemia were studied in nondiabetic rats. In untreated diabetes, the neocortical blood-brain barrier permeability for sodium decreased by 20% (5.6 +/- 0.7 versus 7.0 +/- 0.8 X 10(5) ml/g/s) as compared to controls. Intravenous infusion of 50% glucose for 2 h was associated with a decrease in the blood-brain barrier permeability to sodium (5.4 +/- 1.2 X 10(5) ml/g/s), whereas rats treated with an inhibitor of insulin-secretion (SMS 201-995, a somatostatin-analogue) had normal sodium permeability (7.3 +/- 2.0 X 10(5) ml/g/s). Acute insulin treatment of diabetic rats normalized the sodium permeability within a few hours as compared to a separate control group (7.7 +/- 1.1 versus 6.9 +/- 1.4 X 10(5) ml/g/s). To elucidate whether the abnormal blood-brain barrier passage is caused by a metabolic effect of glucose or by the concomitant hyperosmolality, rats were made hyperosmolar by intravenous injection of 50% mannitol. Although not statistically significant, blood-brain barrier sodium permeability increased in hyperosmolar rats as compared to the control rats (8.3 +/- 1.0 and 7.0 +/- 1.9 X 10(5) ml/g/s, respectively). It is concluded that either hyperglycemia per se or a glucose metabolite is responsible for the blood-brain barrier abnormality which occurs in diabetes. Further, we suggest that the specific decrease of sodium permeability could be the result of glucose-mediated inhibition of the Na+K+-ATPase localized at the blood-brain barrier.
为了探究实验性糖尿病中血脑屏障钠转运变化的发病机制，在非糖尿病大鼠中研究了高血糖和低胰岛素血症的影响。与对照组相比，未经治疗的糖尿病大鼠新皮质血脑屏障对钠的通透性降低了20%（5.6±0.7对7.0±0.8×10⁵ml/g/s）。静脉输注50%葡萄糖2小时与血脑屏障对钠的通透性降低有关（5.4±1.2×10⁵ml/g/s），而用胰岛素分泌抑制剂（SMS 201-995，一种生长抑素类似物）治疗的大鼠钠通透性正常（7.3±2.0×10⁵ml/g/s）。与单独的对照组相比，对糖尿病大鼠进行急性胰岛素治疗在数小时内使钠通透性恢复正常（7.7±1.1对6.9±1.4×10⁵ml/g/s）。为了阐明血脑屏障异常通道是由葡萄糖的代谢作用还是由伴随的高渗状态引起的，通过静脉注射50%甘露醇使大鼠处于高渗状态。与对照大鼠相比，高渗大鼠的血脑屏障钠通透性虽无统计学意义但有所增加（分别为8.3±1.0和7.0±1.9×10⁵ml/g/s）。得出的结论是，高血糖本身或葡萄糖代谢产物是糖尿病中发生的血脑屏障异常的原因。此外，我们认为钠通透性的特异性降低可能是葡萄糖介导的位于血脑屏障的Na⁺K⁺-ATP酶抑制的结果。
