Fernández-Tresguerres Hernández Jesús A
An R Acad Nac Med (Madr). 2004;121(1):157-76; discussion 176-9.
In a previous communication to the RANM two years ago, some data were presented supporting the role of GH, melatonin and estrogens in the prevention of aging of bone, liver metabolism and vascular activity. Additional data were presented about the beneficial effect of these hormones on the Central nervous System (CNS). In the present communication results obtained since that time on the CNS, the immunitary system and the skin will be presented. A total of 140 male and female rats have been investigated. Animals have been decapitated every 6 months starting with 2 and finishinf with 24 months. Another group of 64 rats from both sexes has been submitted to different treatments over 10 weeks, between 22 and 24 months of age. Males have been treated with GH and melatonin. Females were divided in two groups: intact and castrated at 12 months of age. The first group was treated with GH and melatonin and the second with these two and additionally with estradiol and with Phytosoya. Total number of neurones in the hilus of the dentate gyrus has been counted in Nissl stained cerebral cuts. Neurogenesis was estimated by staining with BrdU. Immunitary function was estimated measuring NK activity, chemiotaxis and lymphoproliferative activity in response to Concanavaline A in cultures of leucocytes obtained from axillary nodes and spleen of the animals as well as liberation of IL2 to the medium. An age dependent reduction in the number of neurones has been registrated in male and female rats, without influence of the ovariectomy. A dramatic reduction in neurogenesis has been also detected in both sexes. GH stimulates total number of neurones but does not modify neurogenesis, so a reduction in apoptosis has been considered. This seems to be supported by the reduction in nucleosomes and the increase in Bcl2 observed in cerebral homogenates. Immunitary functions show an age dependent reduction that gets worse with ovariectomy. GH treatment enhances all affected functions as well as estrogens and in some cases melatonin. The skin is also deteriorated by age and that is translated in a reduction of epidermal thickness, an increase in dermical fat and a lowering in the numer of ibroblasts. All these alterations are recovered with GH and melatonin. Keratinocytes from old animals in culture show an increase in nucleosomes nd a reduction in Bcl2 that is restaured with GH and melatonin.
两年前,在提交给皇家澳大利亚内科医师学会的一份报告中,我展示了一些数据,支持生长激素、褪黑素和雌激素在预防骨骼衰老、肝脏代谢及血管活性方面的作用。还展示了这些激素对中枢神经系统(CNS)有益作用的其他数据。在本报告中,将呈现自那时以来在中枢神经系统、免疫系统和皮肤方面所获得的研究结果。总共对140只雄性和雌性大鼠进行了研究。从2个月大开始,每隔6个月对动物进行断头处死,直至24个月大。另一组64只雌雄大鼠在22至24个月大时接受了为期10周的不同处理。雄性大鼠接受生长激素和褪黑素治疗。雌性大鼠分为两组:一组在12个月大时保持完整,另一组在12个月大时进行去势。第一组接受生长激素和褪黑素治疗,第二组除接受这两种激素外,还额外接受雌二醇和植物大豆提取物治疗。在尼氏染色的脑切片中对齿状回门区的神经元总数进行了计数。通过用溴脱氧尿苷(BrdU)染色来评估神经发生情况。通过测量从动物腋窝淋巴结和脾脏获取的白细胞培养物中对刀豆球蛋白A的自然杀伤(NK)活性、趋化性和淋巴细胞增殖活性,以及白细胞介素2(IL2)释放到培养基中的情况来评估免疫功能。已记录到雄性和雌性大鼠的神经元数量随年龄增长而减少,卵巢切除术对此没有影响。在两性中还检测到神经发生显著减少。生长激素可刺激神经元总数增加,但不改变神经发生情况,因此认为这是由于细胞凋亡减少所致。这似乎得到了脑匀浆中核小体减少和Bcl2增加的支持。免疫功能呈现出随年龄增长而下降的趋势,卵巢切除术后情况会更糟。生长激素治疗可增强所有受影响的功能,雌激素以及在某些情况下褪黑素也有此作用。皮肤也会因年龄增长而变差,表现为表皮厚度减少、真皮脂肪增加和成纤维细胞数量减少。所有这些改变都可通过生长激素和褪黑素恢复。培养的老年动物角质形成细胞显示核小体增加且Bcl2减少,而生长激素和褪黑素可使其恢复。