Sonntag W E, Lynch C D, Cooney P T, Hutchins P M
Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1083, USA.
Endocrinology. 1997 Aug;138(8):3515-20. doi: 10.1210/endo.138.8.5330.
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 area) 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 from 15.53 +/- 1.08 to 9.49 +/- 0.62 endpoints/mm2 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/mm2 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, s.c., 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.
多项报告表明，脑血流量会随着年龄增长而减少，这可能导致在衰老动物和人类中发现的神经退行性变化。由于生长激素（GH）和胰岛素样生长因子1（IGF-1）会随着年龄增长而减少，且在血管维持和重塑中发挥重要作用，我们推测脑血流量的减少与GH和IGF-1水平下降导致的脑血管稀疏有关。使用慢性颅骨开窗室对5、13和29月龄的棕色挪威大鼠以及费希尔344/棕色挪威大鼠的血管密度（血管数量/皮质表面积）进行测量，该开窗室可用于观察皮质表面及其相应的脉管系统。并与血浆IGF-1水平进行相关性分析。在棕色挪威大鼠中，7月龄和29月龄动物的小动脉密度分别从15.53±1.08降至9.49±0.62个端点/mm²（P<0.05）。小动脉吻合也出现减少[7月龄和29月龄动物分别从3.05±0.21降至1.42±0.24个连接/mm²（P<0.05）]。静脉密度并未随年龄下降。在费希尔344/棕色挪威大鼠中也观察到了类似变化。在血管测绘时，皮质表面小动脉数量与血浆IGF-1水平相关（r = 0.772，P<0.05），对30月龄动物皮下注射牛GH（0.25mg/kg，每日两次，共35天）可使血浆IGF-1和皮质小动脉数量均增加。这些数据表明：1）皮质表面的血管密度随年龄下降；2）血管密度与血浆IGF-1水平相关；3）对老年动物注射GH可增加皮质血管密度。我们得出结论，GH和IGF-1在血管密度随年龄下降过程中起重要作用，并表明血管密度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。
