| Abstract: | 老化會引發相關的退化性疾病，並且可能導致沈重的醫療負擔，因此深入研究老化的相關機制，將可藉以研發治療老化相關疾病更有效的方法。長期給予齧齒類動物注射D-galactose可以誘發動物出現許多生理及行為症狀，這些症狀與自然老化所出現的症狀相似。由於D-galactose所造成的加速老化現象也會伴隨出現氧化傷害(oxidative damage)及神經退化現象，因此D-galactose處理之動物不僅適合用以探討老化的機制，並且可以用以研究相關藥物的神經保護效果。俄羅斯科學院新西伯利亞分院細胞與基因學研究所(Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia)選育出一種具有加速老化基因的OXYS大鼠，這種大鼠會出現加速老化的現象導致壽命減短。OXYS大鼠所出現的老化病理變化與人類的老化疾病相似，而且近年使用磁震造影技術(magnetic resonance imaging; MRI)也證實 OXYS大鼠的神經退化現象。上述OXYS大鼠的老化現象可以經由抗氧化藥物加以改善。薯蕷皂?(diosgenin)是山藥所含的一種重要活性成分，具有抗氧化之功能，也可以改善D-galactose誘發老化所造成的空間記憶缺陷，顯示diosgenin可能可以改善老化相關疾病。本項3 年期之研究計畫主要目的在於比較導致OXYS 大鼠老化與D-galactose (150 mg/kg/day, i.p.)誘發Wistar 大鼠老化的共同機制，並且探討diosgenin (10 或50 mg/kg/day) 長期處理之抗老化功能。逐年之研究工作如下：第一年：探討並比較OXYS 大鼠與 D-galactose 長期處理誘發老化Wistar 大鼠之工作記憶、認知功能、性動機、生殖內分泌活性、氧化壓力與神經退化現象。第二年：探討diosgenin 長期處理對OXYS 大鼠與 D-galactose 長期之Wistar 大鼠的行為表現、器官生化功能、氧化壓力與神經退化之影響。第三年：以組織化學與MRI 技術測量活體OXYS 大鼠與D-galactose 處理之Wistar 大鼠其腦部結構的差異及diosgenin 長期處理之效果。
Aging is associated with degenerative diseases, and may result in a heavy medical burden for the society. Understanding the aging mechanism would provide an opportunity for developing a better treatment for aging-related diseases. Chronic administration of D-galactose in rodents induces physiological and behavioral changes that resemble natural aging. Because D-galactose-induced senescence acceleration is accompanied by oxidative damage and neurodegeneration, it is an ideal model for studying the aging mechanisms and for testing neuroprotective agents. Another promising model for studying aging processes is OXYS rat strain with genetically defined accelerated senescence. This strain was produced in the Institute of Cytology and Genetics SB RAS (Novosibirsk, Russia) with selective breeding of Wistar rats. OXYS rats show degenerative features which can be regarded as a syndrome of accelerated senescence. The OXYS rats are known for shortened lifespan and an early development of age-related pathological phenotypes similar to several geriatric disorders observed in humans. Further, neurodegeneration in the brain of OXYS rats has been identified by magnetic resonance imaging (MRI). Recently, it has been demonstrated that some aging-related features of OXYS rats are corrected or improved by anti-oxidant drug. Diosgenin, one of the important bio-active ingredients in a Chinese medicine, dioscorea, has long been used as a precursor in manufactory for producing steroid hormones. In addition, diosgenin shows anti-oxidant activity and improves spatial memory in senescent mice induced by D-galactose, suggesting that diosgenin may have beneficial effects on aging animals. The main goals of this 3-year proposal are comparing the aging mechanisms in OXYS rats and in D-galactose (150 mg/kg/day, i.p.)-treated Wistar rats and evaluating chronic effects of diosgenin (10 and 50 mg/kg/day) in the two aging models. The following studies will be conducted: (1) the 1st year: measuring the working memory, cognitive function, sexual motivation, reproductive endocrine activity, oxidative stress, and neurodegeneration in OXYS rats and in D-galactose-induced aging Wistar rats. (2) the 2nd year: exploring chronic effects of diosgenin in OXYS rats and in D-galactose-induced aging Wistar rats. (3) the 3rd year: exploring the brain structure of OXYS and D-galactose-treated Wistar rats by using methods of immunohistochemistry and MRI, and comparing the function of chronic diosgenin treatment in these rats. |
