Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1
Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1
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DOI：
10.1210/en.138.8.3515
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发表时间：
1997-08-01
期刊：
影响因子：
4.8
通讯作者：
Hutchins, PM
中科院分区：
文献类型：
--
作者：
Sonntag, WE;Lynch, CD;Hutchins, PM
一些报告表明，脑血流量随着年龄的增长而减少，可能会导致老年动物和人类的神经退行性变化。由于GH和胰岛素样生长因子1（IGF-1）随着年龄的增长而减少，并且在血管维持和重塑中具有重要作用，因此我们推测脑血流量的减少与GH和IGF-1减少导致的脑血管稀疏有关。使用允许观察皮质表面及其相应脉管系统的慢性颅窗室在 5、13 和 29 个月龄时测量 Brown-Norway 和 Fisher 344/Brown-Norway 大鼠的血管数量/皮质表面积。与血浆 IGF-1 水平建立相关性。在 Brown-Norway 大鼠中，小动脉密度降低 ii om 15.53 7 月龄和 29 月龄动物中分别为 +/- 1.08 至 9.49 +/- 0.62 个端点/mm(2) (P < 0.05)。在小动脉吻合中也观察到下降 [7 月龄和 29 月龄动物中为 3.05 +/- 0.21 至 1.42 +/- 0.24 个连接/mm(2) (P < 0.05)。 0.05)]，在 Fisher 344/Brown-Norway 大鼠中观察到类似的变化。皮层表面小动脉的数量与血管绘图时的血浆 IGF-1 水平相关（r = 0.772，P < 0.05），并且向 30 月龄动物注射牛 GH（0.25 mg/kg，皮下注射，每天两次，持续 35 天）。血浆IGF-1和皮质小动脉的数量这些数据表明：1）皮质表面的血管密度随着年龄的增长而降低； 2）血管密度与血浆IGF-1水平相关； 3) 注射 GH 会增加老年动物的皮质血管密度。我们得出的结论是，GH 和 IGF-1 在血管密度随年龄下降的过程中发挥着重要作用，并表明血管密度的下降可能对与年龄相关的脑血流量和脑功能下降具有重要影响。
Several reports have demonstrated that cerebral blood flow decreases with age and may contribute to neurodegenerative changes found in aging animals and man. Because GH and insulin-like growth factor 1 (IGF-1) decrease with age and have an important role in vascular maintenance and remodeling, we hypothesized that the decrease in cerebral blood flow is associated with a rarefaction of cerebral blood vessels resulting from a decline in GH and IGF-1. Measurements of vascular density (number of vessels/cortical surface areal in both Brown-Norway and Fisher 344/Brown-Norway rats were made at 5, 13, and 29 months of age using chronic cranial window chambers that allowed viewing of the cortical surface and its corresponding vasculature. Correlations were made with plasma levels of IGF-1. In Brown-Norway rats, arteriolar density decreased ii om 15.53 +/- 1.08 to 9.49 +/- 0.62 endpoints/mm(2) in 7- and 29-month-old animals, respectively (P < 0.05). A decline was observed also in arteriolar anastomoses [3.05 +/- 0.21 to 1.42 +/- 0.24 connections/mm(2) in 7- and 29-month-old animals (P < 0.05)]. Venular density did not decrease with age. Similar changes were observed in Fisher 344/Brown-Norway rats. The number of cortical surface arterioles was correlated with plasma IGF-1 levels at the time of vascular mapping (r = 0.772, P < 0.05), and injection of bovine GH (0.25 mg/kg, sc, twice daily for 35 days) to 30-month-old animals increased both plasma IGF-1 and the number of cortical arterioles. These data indicate that: 1) vascular density on the surface of the cortex decreases with age; 2) Vascular density is correlated with plasma levels of IGF-1; and 3) injection of GH increases cortical Vascular density in older animals. We conclude that GH and IGF-1 have an important role in the decline in vascular density with age and suggest that decreases in vascular density may have important implications for the age-related decline in cerebral blood flow and brain function.