Amenta F, Ferrante F, Mancini M, Sabbatini M, Vega J A, Zaccheo D
Sezione di Anatomia Umana, Istituto di Farmacologia, Università di Camerino, Camerino, Italy.
Mech Ageing Dev. 1995 Jan 31;78(1):27-37. doi: 10.1016/0047-6374(94)01513-l.
The effects of treatment with the dihydropyridine Ca+2 antagonist darodipine (PY 108-068) on age-related changes in the cerebral capillary network was studied using alkaline phosphatase histochemistry with quantitative image analysis. The investigation was performed on male Wistar rats of 12 months (adult reference group) and 27 months. The 27-month-old rats consisted of two groups, the first of control untreated animals and the second of rats receiving an oral dose of 5 mg/kg/day of darodipine from the 21st to the 27th month. The cerebral areas examined included the frontal cortex, the occipital cortex, Ammon's horn of the hippocampus, and the dentate gyrus. The number and the average length of alkaline phosphatase-positive capillaries were decreased in old rats, when compared with adult rats. The intercapillary distance, which is considered as a sensitive parameter for capillary density was increased in aged rats in comparison to adult rats. The capillary diameter was increased slightly or unchanged in old rats. The Ammon's horn and the frontal cortex were the cerebral areas most affected by age-dependent changes of the capillary network. Treatment with darodipine increased the number and the average length of alkaline phosphatase-reactive capillaries and reduced the intercapillary distance and the diameter of cerebral capillaries in old rats. The pericapillary microenvironment of the Ammon's horn was the most sensitive to treatment with darodipine. The above results showed that treatment with darodipine is capable of counteracting some microvascular changes occurring in the brain of aged rats. This suggests that the blockade of dihydropyridine-type Ca2+ channels has a positive effect on the brain microvascular system and may counteract the impairment of pericapillary microenvironment occurring with aging.
采用碱性磷酸酶组织化学结合定量图像分析的方法，研究了二氢吡啶类钙离子拮抗剂达罗地平（PY 108 - 068）对脑毛细血管网络年龄相关变化的影响。研究对象为12个月大的雄性Wistar大鼠（成年参照组）和27个月大的雄性Wistar大鼠。27个月大的大鼠分为两组，第一组为未治疗的对照动物，第二组为从第21个月至第27个月口服5 mg/kg/天达罗地平的大鼠。所检查的脑区包括额叶皮质、枕叶皮质、海马的角回和齿状回。与成年大鼠相比，老年大鼠碱性磷酸酶阳性毛细血管的数量和平均长度减少。作为毛细血管密度敏感参数的毛细血管间距，与成年大鼠相比，老年大鼠有所增加。老年大鼠的毛细血管直径略有增加或无变化。角回和额叶皮质是受毛细血管网络年龄依赖性变化影响最大的脑区。达罗地平治疗增加了老年大鼠碱性磷酸酶反应性毛细血管的数量和平均长度，并减小了脑毛细血管的间距和直径。角回的毛细血管周围微环境对达罗地平治疗最为敏感。上述结果表明，达罗地平治疗能够抵消老年大鼠脑中发生的一些微血管变化。这表明二氢吡啶型钙离子通道的阻断对脑微血管系统有积极作用，并可能抵消衰老过程中发生的毛细血管周围微环境的损害。
