McCuskey P A, McCuskey R S
Microcirc Endothelium Lymphatics. 1984 Apr;1(2):221-44.
The cerebral microvasculature of rats rendered diabetic with streptozotocin (75 mg/kg) and vehicle-treated controls paired for age and sex were studied using in vivo and electron microscopic methods at intervals from two weeks to 12 months after induction of diabetes mellitus. By one month, the pial vessels of diabetics were dilated and tortuous; and, the vasoconstrictive responses of arterioles and venules to local increases of PO2 in the artificial CSF bathing these vessels was reduced as was the linear velocity of blood flow. Increased arterio-venous shunting also was observed. By five months the responsiveness to locally increased levels of PO2 was further reduced from control values of 49.9% +/- 5 (SEM) to 6.9% +/- 1.8 (SEM) in arterioles and from 11.5% +/- 2.1 (SEM) to 2.6% +/- 0.7 (SEM) in venules. No further significant change in responsiveness was measured from five to twelve months. At 5 months, the functional changes were no longer reversible; and focal changes were noted in the thickness and density of the vascular basement membrane. Astrocytic end feet were greatly swollen and contained mitochondria having longitudinal rearrangement of their cristae. Basement membranes contained nodules of electron-lucent material which impinged on degenerating smooth muscle cells, pericytes and astrocytes. In some sites these cells appeared to be replaced by an amorphous material laced with collagen fibrils. By 11 months, these focal lesions were more frequent and more pronounced. Additional cellular replacement had taken place which resulted in greatly widened basement membranes which varied in density and content. The ultrastructure of endothelial cells was not noticeably altered except for presence of numerous cytoplasmic vesicles. The tight interendothelial junctions appeared to be intact even though dramatic changes had taken place perivascularly. These architectural and functional changes in the microvasculature are suggested to result not only from metabolic defects in the vascular wall, but also as a response to a relative hypoxia of the brain during the diabetic state.
采用体内和电子显微镜方法，对用链脲佐菌素（75毫克/千克）诱导糖尿病的大鼠以及与之年龄和性别匹配的赋形剂处理对照组大鼠的脑微血管进行了研究，观察时间为糖尿病诱导后两周至12个月。到一个月时，糖尿病大鼠的软脑膜血管扩张且迂曲；并且，小动脉和小静脉对人工脑脊液中局部PO2升高的血管收缩反应减弱，血流线速度也降低。还观察到动静脉分流增加。到五个月时，小动脉对局部PO2升高水平的反应性从对照组的49.9%±5（标准误）进一步降低至6.9%±1.8（标准误），小静脉从11.5%±2.1（标准误）降低至2.6%±0.7（标准误）。从五个月到十二个月，反应性没有进一步的显著变化。在五个月时，功能变化不再可逆；并且在血管基底膜的厚度和密度方面出现了局灶性变化。星形胶质细胞终足明显肿胀，线粒体嵴呈纵向重排。基底膜含有电子透明物质结节，这些结节压迫退化的平滑肌细胞、周细胞和星形胶质细胞。在一些部位，这些细胞似乎被含有胶原纤维的无定形物质所取代。到11个月时，这些局灶性病变更加频繁和明显。发生了额外的细胞替代，导致基底膜大大增宽，其密度和成分各不相同。除了存在大量细胞质小泡外，内皮细胞的超微结构没有明显改变。尽管血管周围发生了显著变化，但内皮细胞间紧密连接似乎完好无损。微血管的这些结构和功能变化被认为不仅是由于血管壁的代谢缺陷，也是糖尿病状态下大脑相对缺氧的一种反应。
