PERMEABILITY OF BLOOD-BRAIN AND BLOOD NERVE BARRIERS IN EXPERIMENTAL DIABETES-MELLITUS IN THE ANESTHETIZED RAT
PERMEABILITY OF BLOOD-BRAIN AND BLOOD NERVE BARRIERS IN EXPERIMENTAL DIABETES-MELLITUS IN THE ANESTHETIZED RAT
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DOI：
10.1113/expphysiol.1991.sp003551
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发表时间：
1991-11-01
影响因子：
2.7
通讯作者：
PINTER, GG
中科院分区：
文献类型：
--
作者：
BRADBURY, MWB;LIGHTMAN, SL;PINTER, GG
体重约160克的大鼠用链脲佐菌素诱发糖尿病。与年龄匹配的对照组保持糖尿病长达14个月，定期监测血糖。一半的糖尿病大鼠和对照组大鼠在饮食中服用了醛糖还原酶抑制剂Ponalrest at。分别于术后3周、6~7个月和13~14个月测定脑区、视神经和坐骨神经的血管通透性，维持血流中的放射性示踪剂I-125-白蛋白(100分钟)、[C-14]蔗糖(60分钟)和I-131-白蛋白(5分钟)，然后在终止时进行组织取样和计数。~(131)I-白蛋白测定残余血管内血浆。糖尿病持续13-14周，在视神经或坐骨神经的8个不同脑区，微血管的蔗糖通透性没有明显增加。糖尿病3周时，各脑区和视神经的蔗糖通透性均较正常对照组降低。血管外白蛋白进入脑和视神经的不同区域不明显，对糖尿病不敏感，但在下丘脑和视神经中随着糖尿病病程的延长而升高。在坐骨神经中，糖尿病使血管外白蛋白分布明显增加，但对蔗糖通透性无明显影响。在饮食中使用的水平上，Ponalrest降低了糖尿病坐骨神经中山梨醇的含量，但不能再次保护增加的白蛋白通透性。
Diabetes was induced with streptozotocin in rats weighting about 160 g. These were maintained with age-matched controls for up to 14 months, blood glucose being periodically monitored. Half the diabetic and control rats received the aldose reductase inhibitor, Ponalrestat, in their diet. At 3 weeks, 6-7 months and 13-14 months, the vascular permeability in regions of brain, and in optic and sciatic nerves, were measured by maintaining radiotracers in the bloodstream - I-125-albumin (100 min), [C-14]sucrose (60 min) and I-131-albumin (5 min) - followed by tissue sampling and counting at termination. I-131-albumin estimated residual intravascular plasma. Diabetes of up to 13-14 weeks caused no measurable increase in the sucrose permeability of microvessels in eight different brain regions, in optic or in sciatic nerve. At 3 weeks of diabetes, sucrose permeability in all brain regions and in optic nerve was reduced relative to that in controls. Extravascular albumin entry into different regions of brain and optic nerve was insignificant and insensitive to diabetes, except in the hypothalamus and optic nerves where it was raised with increasing duration of diabetes. In sciatic nerve, extravascular albumin distribution was markedly increased by diabetes, but sucrose permeability was not demonstrably affected. At the level used in the diet, Ponalrestat reduced the sorbitol content of diabetic sciatic nerve but did not protect again the increased permeability to albumin.