【作者】 杨靖；

【导师】 李德新；

【作者基本信息】 辽宁中医学院 ， 中医基础理论， 2004， 博士

【摘要】 二十世纪末的1999年，是联合国大会确定的“国际老年人年”，这表明老龄问题已引起国际社会的普遍关注和重视。加强衰老机理与延缓衰老的研究是新世纪医学领域的重大研究课题。中医药在延缓衰老方面有着广阔的应用前景。 中医学认为，人体衰老与脏腑经络、气血阴阳及精气神密切相关。脏腑之中尤以先天之本肾和后天之本脾关系最为密切。脾为后天之本，气血生化之源，主运化，主升清，与人体生长壮老已息息相关。脾虚是衰老的起始因素及衰老过程中渐见加重的病理过程，因此健脾可以延缓人体衰老。四君子汤是中医学健脾益气的代表方剂，其药味组成中全部为《神农本草经》之上品，有“轻身延年”之功效。现代药理研究也表明，四君子汤能提高人体抗氧化酶活性，增强免疫功能。本研究在以往研究基础上，根据衰老的自由基学说和端粒学说，进一步观察探讨四君子汤延缓衰老作用机制，为中医药关于脾虚衰老理论提供依据，为把四君子汤作为延缓衰老药开发利用奠定基础。 本研究的主要内容包括： 1、四君子汤对D-半乳糖(D-gal)衰老模型小鼠学习记忆能力的影响 采用小鼠跳台法，观察并记录小鼠呆在安全区的时间(Ts)、呆在错误区的时间(Te)、潜伏期时间(LP)及错误次数(Ne)。 2、四君子汤对D-gal衰老模型小鼠心、脑、肝脏组织超氧化物歧化酶(SOD)活性的影响 采用MTT法，检测了各组小鼠心、脑、肝脏组织SOD活性，经统计学处理，比较了各组小鼠心、脑、肝脏组织SOD活性的变化。摘要 3、四君子汤对D一gal衰老模型小鼠肝脏组织谷眺甘肤过氧化物酶(GSH一]〕x)活性的影响 采用DINB法，检测了各组小鼠肝脏组织GSH一Px活性，经统计学处理，比较了各组小鼠肝脏组织GSH一Px活性的变化。 4·四君子汤对D一gal衰老模型小鼠心、脑、肝脏组织脂质过氧化物的分解产物丙二醛(MDA)含量的影响 采用TBA比色法，检测了各组小鼠心、脑、肝脏组织MDA含量，经统计学处理，比较了各组小鼠心、脑、肝脏组织MDA含量的变化。 5、四君子汤对D一gal衰老模型小鼠心、脑、肝、胸腺组织端粒酶活性的影响 采用PCR一ELISA法，检测了各组小鼠心、脑、肝、胸腺组织端粒酶活性，经统计学处理，比较了各组小鼠心、脑、肝、胸腺组织端粒酶活性的变化。 6、四君子汤对D一gal衰老模型小鼠脑组织形态学的影响 采用DMBA45O型生物数码显微图象分析系统，观察了各组小鼠脑海马部位形态学的变化。研究结果表明: 1、四君子汤各剂量组均能改善D一gal衰老模型小鼠的学习记忆能力(Ts延长·Ne减少)，尤其是高剂量组能明显提高D一gal衰老模型小鼠的学习记忆能力。 2、四君子汤各剂量组均能提高D一gal衰老模型小鼠心、脑、肝脏组织SOD活性，尤其是高剂量组能使SOD值接近正常对照组的水平。 3、四君子汤各剂量组均能提高D一gal衰老模型小鼠肝脏组织GSH一Px的活性，高剂量的四君子汤能明显提高D一gal衰老模型小鼠肝脏组织中GSH一Px的活性，可致接近正常对照组的水平。 4·四君子汤各剂量组均能减少D一gal衰老模型小鼠心、脑、肝脏组织中MDA的含量，其中中、高剂量组对心脏组织中MDA含量变化影响明显，可致接近正常水平;在脑和肝脏组织中，高剂量组的作用显著，中、低剂量组的作用稍差。 5、四君子汤能明显提高D一gal衰老模型小鼠脑及胸腺组织端粒酶活性;对心脏组织端粒酶活性有提高的趋势，但作用不显著;而对肝脏组织端粒酶活性没有影响。 6、四君子汤能改善D一gal衰老模型小鼠脑组织发生的衰老性改变。 四君子汤延缓衰老作用的可能机制: 1、通过提高机体抗氧化酶(S OD、GSH一Px)的活性，减少MDA的生成，从而摘要减轻自由基对机体的氧化损伤，达到延缓衰老的目的。 2、通过提高模型小鼠心、脑、胸腺组织中端粒酶活性，维持端粒长度和稳定或减缓其缩短速率，从而达到延缓细胞衰老的目的。更多还原

【Abstract】 The year of 1999 is the International Old Age Year designated by the UN Conference. This indicates that the problem of old age has aroused the universal concern and emphasis of the international society. To enforce the research on the principle of aging and delaying aging is an important research subject in the medical field in the new century. Traditional Chinese medicine has a bright future in delaying aging.Traditional Chinese Medicine thinks that people’s aging is closely related to Zang, Fu, channels, collateral. Qi, blood. Yin. Yang and the vigor. Between channels and collateral, kidney and spleen are most related to each other. Spleen is the source of Qi and blood. It is responsible for carrying and sending up and is closely related to the body’s growth and aging. The deficiency of the spleen is the cause of aging and is also the pathological process in aging. As a resuct. invigorating spleen can delay aging. Decoction of Four Noble Drugs is the representative recipe of strengthening the spleen and replenishing Qi. Its elements are all superior ones included in Shen Nong’s Herbal Classic and have the function of expelling the diseases and lengthening one’s life. Modern pathological research also proves that Decoction of Four Noble Drugs can promote the activity of antioxidase of the body and strengthen the immunity of the body. Based on previous research as well as the theory of free radical and the theory of telemeter, this article does further research on the Decoction of Four Noble Drugs in its delaying aging mechanism so as to provide proof for the theory of deficiency of spleen and aging and therefore lay a good basis for developing the Decoction of Four Noble Drugs as a drug of delaying aging.The main contents of the research.I. The influence of the Decoction of Four Noble Drugs on the memorizing ability of mice in the D-gal aging model.Use the mice jumping-platform method and observ and record the time that the mice stay in the safe area, in the wrong area, the latent time and the number of mistakes.II. The influence of Decoction of Four Noble Drugs on the activity of superoxide dixmutase in the tissues of the mice’s heart, brain, and liver.Use the MTT method and test the SOD activity of the tissues of the mice’s heart, brain and liver and compare statistically the SOD activity changes of the tissues of the heart, brain and liver of different groups of mice.III. The influence of the Decoction of Four Noble Drugs on the activity of gluts throne peroxides in the mice’s liver tissues in the D-gal aging model.Use the DTNB method and test the GSH-Px activity in the liver tissues of various groups of mice. Then compare statistically the GSH-Px activity changes in the liver tissues of various groups of mice.IV. The influence of the Decoction of Four Noble Drugs on lipid peroxides decomposed product, i. e MDA contentUse the TBA colorimeter and test the MDA content of the tissues of heart, brain and liver of various groups of mice.V. The influence of the Decoction of Four Noble Drugs on telemeter enzyme activity of the tissues of the heart, brain, liver and thymus gland of the mice in the D-gal aging model.Use the PCR-ELISA method and test the telemeter enzyme activity of the telemeter enzyme activity of the tissues of the heart, brain, liver and thymus gland of the mice and compare statistically the changes of the telemeter enzyme activity of the tissues of the heart, brain, liver and thymus gland of the various groups of mice.VI. The influence of the Decoction of Four Noble Drugs on the mice’s brain tissue morphology in the D-gal aging model.The research result shows that:I. Different dosage groups of the Decoction of Four Noble Drugs can improve the mice’s learning and memorizing ability, especially improve the mice’s learning and memorizing ability in the high-dosage group in the D-gal aging model.II. Different dosage groups of the Decoction of Four Noble Drugs can improve the mice’s heart, brain and liver tissue SOD activity, especially the high-dosage whic更多还原