刺五加苷延缓衰老作用机理研究
|
摘要
刺五加由于含有多种的天然活性成分,且无毒副作用,自古就倍受人们青睐。随着生物活性物质分离纯化技术的发展,人们目前已经开展了大量关于刺五加活性成分的分离提取和结构鉴定方面的研究,刺五加苷就是人们利用现代化手段提取从刺五加中提取的天然活性物质。
本课题给成年SD大鼠连续腹腔注射D-半乳糖建立衰老动物模型后,利用不同浓度刺五加苷作用于该模型,以维生素E作为阳性对照,从机能和形态两个方面研究刺五加苷是否具有延缓衰老的作用。在得出刺五加苷具有延缓衰老作用的基础上,结合目前世界上比较公认的自由基、免疫、端粒长度、细胞凋亡衰老学说,从体内、外两个方面研究刺五加苷延缓衰老的机理。在体内,研究了刺五加苷对衰老大鼠抗氧化能力、免疫功能、p16蛋白和对衰老相关-β-半乳糖苷酶的影响;在体外,利用具有自发凋亡的胸腺细胞作为模型,观察了刺五加苷对小鼠胸腺细胞凋亡的作用。由于衰老过程涉及机体各个系统、不同结构层次,因此本研究在整体水平、组织器官水平、细胞水平以及分子水平,分别研究了刺五加苷延缓衰老的机制。
本研究的研究结果有以下几方面:
(1)D-半乳糖致衰老模型构建成功。模型大鼠组织中SOD、GSH-Px活性下降,iNOS活性升高,MDA、NO浓度升高,T淋巴细胞增殖功能下降,血清IL-2浓度下降,IL-6浓度和TNF-α浓度升高,组织SA-β-gal活性增强,p16蛋白表达增加。
(2)刺五加苷可以改善衰老大鼠功能。刺五加苷能增加衰老大鼠的胸腺指数和脑指数,增强学习和记忆能力,升高血中HDL-C浓度,降低TG、TC、LDL-C浓度,降低血液粘滞性。高浓度刺五加苷降低TG浓度、增强学习和记忆能力、增加胸腺和脑指数的作用好于维生素E,中、低浓度刺五加苷降低LDL-C作用效果弱于维生素E,低浓度刺五加苷改善大鼠学习和记忆能力作用也弱于维生素E。
(3)高浓度刺五加苷可以延缓卵巢组织形态衰老。刺五加苷作用后衰老大鼠卵泡细胞轮廓清,线粒体损伤减轻,核肿胀缓解,常染色质分布均匀,中、低浓度刺五加苷和维生素E作用后细胞器多种退行性改变仍很严重。
刺五加苷可延缓神经细胞退行性改变。高浓度刺五加苷可使神经细胞轮廓清晰,核膜完整光滑,常染色质分布均匀,但其对神经细胞质水肿、线粒体嵴损伤改善仍不明显,中、低浓度刺五加苷和维生素E作用后细胞器退行性改变较严重。
各浓度刺五加苷都可以抑制肝细胞退行性改变。刺五加苷可以使肝细胞轮廓清晰、线粒体形态基本完好,高浓度刺五加苷作用效果最好,胞质内可见大量粗面内质网呈板层状排列,线粒体丰富,糖原数量多。
(4)刺五加苷具有抗氧化作用。各浓度刺五加苷都可以升高衰老大鼠组织SOD、GSH-Px活性,抑制iNOS活性,降低MDA、NO浓度。高浓度刺五加苷提高GSH-Px、SOD活性、降低MDA和NO浓度、抑制iNOS活性的作用强于维生素E,中浓度提高GSH-Px活性、降低MDA浓度作用也强于维生素E,低浓度刺五加苷降低MDA和NO浓度作用弱于维生素E。
(5)刺五加苷具有延缓免疫衰老作用。中、高浓度刺五加苷都可以提高衰老大鼠T淋巴细胞增殖功能和IL-2浓度,降低IL-6浓度,高浓度还可以降低TNF-α浓度。高浓度刺五加苷提高T淋巴细胞增殖功能和IL-2浓度作用,降低IL-6和TNF-α浓度作用都强于维生素E;中浓度提高T淋巴细胞增殖功能和IL-2浓度作用也强于维生素E,低浓度刺五加苷调节机体细胞免疫功能的作用与维生素E比较差异不明显。
(6)刺五加苷具有抑制衰老相关-β-半乳糖苷酶活性和降低p16蛋白表达的作用。中、高浓度刺五加苷具有抑制大鼠衰老相关-β-半乳糖苷酶活性,降低组织p16蛋白表达的作用,低浓度只能抑制衰老相关-β-半乳糖苷酶活性。中、高浓度刺五加苷抑制组织衰老相关-β-半乳糖苷酶活性,降低组织p16蛋白表达作用强于维生素E;低浓度抑制组织SA-β-gal活性作用弱于维生素E。
(7)小鼠胸腺细胞随着培养时间延长,会发生时间依赖性凋亡,表现为S期和G_2/M期细胞比例减少,增值能力下降。50、100μmol/L刺五加苷可以增加胸腺小鼠细胞增值指数、抑制细胞凋亡,作用好于维生素E;20μmol/L刺五加苷能抑制细胞凋亡,作用效果与维生素E没有显著差异。
通过以上研究,本课题得出刺五加苷具有延缓机体衰老的作用,其作用机理与刺五加苷提高机体抗氧化能力、增强细胞免疫功能、降低p16蛋白表达、促进胸腺细胞增殖、抑制细胞凋亡相关。
Ciwujia containing a wide range of natural active ingredients,and non-toxic side effects, with the advantages of both temporary and permanent cures,people on the popular favor since ancient times.With the isolation and purification of bioactive substances in the development of technology,people have carried out a large number of active ingredients on the ciwujianoside and structural identification studies.Ciwujianoside is the use of modern means of extracting ciwujia from natural active substances.
In this study,by continuous subcutaneous injecting D-galactose to adult SD rats establish an animal model of aging,using of different concentrations ciwujianoside in rats,studying anti-aging from both functional and morphological.The result is ciwujianoside with anti-aging.Therefore,we research the current aging theory,such as the free radical theory,the immune theory of aging,telomere length theory,theory of apoptosis,study the mechanism of anti-aging ciwujianoside both in vitro and in vivo.
In vivo,the studied is carried out by ciwujianoside on antioxidant capacity,immune function,p16 protein and senescence-associated-β-galactosidase impact in aging rats.In vitro, the studied is carried out by the ciwujianoside on the role ofapoptosis in thymocytes,with the spontaneous apoptosis of thymocytes as a model.As the aging process involves various body systems,the study relate to the level of different structures,the mechanisms of ciwujianoside anti-aging of in the overall level,the level of tissues and organs,cells and molecular level.
The results of this study are the following:
(1) The D-gal-induced aging model do not change rat body weight,electrocardiogram, heart rate,WBC,RBC,HGB,PLT,MCV,ALT,AST,TP,ALB,GLO,not change in liver, heart,brain,spleen,kidney tissue vitality tNOS.However,it decrease SOD,GSH-Px activity, increase iNOS activity,MDA,NO concentration increase;T lymphocyte proliferation function,serum IL-2,IL-6 concentrations decrease,TNF-αconcentrations increase;tissue SA-β-gal activity and p16 protein expression enhance.
(2) Ciwujianoside can increase the rat thymus and brain aging index,and enhance learning and memory capacity,higher blood HDL-C concentration and lower TG,TC,LDL-C concentrations and lower blood viscosity,and high concentrati0ns of ciwujianoside obvious effect better than the low and middle.In addition,the high concentration of ciwujianoside reduct TG concentration,enhance learning and memory capacity,increase thymic index,and the role of the brain better than vitamin E.But effect of enhancing learning and memory capacity in the low concentration lower than that of the vitamin E.
(3) High concentrations of ciwujianoside follicle cells in aging rats could outline a clear and reduce the extent of mitochondrial injury,to alleviate the status of nuclear swelling,so that distribution euchromatin with delay ovarian aging patterns.However,in other concentrations of ciwujianoside and vitamin E,follicles occupy the cytoplasm is obvious edema in follicles,mitochondrial degeneration seen,a variety of cell degenerative changes are still very serious.In addition,high concentrations of ciwujianoside can make the outline of nerve cells in aging rats clear,smooth nuclear membrane integrity,euchromatin distribution, delay nerve cell degeneration,but the cytoplasm of nerve edema,mitochondrial cfistae damage does not improve significantly.
(4) Ciwujianoside can increase the SOD,GSH-Px activity,inhibiting iNOS activity and lower MDA,NO concentration.The role of high concentrations of ciwujianoside results significantly better than middle and low concentration groups,which is the role of a dose-dependent.High concentrations of ciwujianoside on increase T lymphocyte proliferation, IL-2 concentration,IL-6 concentrations,lower TNF-αconcentrations is better than the effect of vitamin E.Middle concentration ciwujianoside in aging rats only increase T lymphocyte proliferation and enhance IL-2 concentration better than vitamin E,The effect of low concentration ciwujianoside reducting MDA and NO concentration is lower than the vitamin E.
(5) Ciwujianoside to postpone the role of immunosenescence in a dose-dependent way.High concentrations of ciwujianoside can delaying immunosenescence by increasing T lymphocyte proliferation,IL-2 concentration,lowing IL-6 and TNF-αconcentrations.Middle concentrations of ciwujianoside increase T lymphocyte proliferation and IL-2 concentration better than vitamin E;Low concentration of ciwujianoside in the regulation of aging cellular immune function in rats is not obvious.High concentrations of ciwujianoside in aging rats increase T lymphocyte proliferation,IL-2 concentration,lower concentrations of IL-6 concentrations,TNF-αconcentrations effects are better than the vitamin E.Low concentration of ciwujianoside in the regulation cellular immune function compare with the vitamin E the difference is not obvious.
(6) Middle and high concentrations of ciwujianoside can inhibit SA-β-gal activity and lower p16 protein expression in a dose-dependent manner.Low concentrations of ciwujianoside only can inhibit SA-β-gal activity.The high and middle concentrations of ciwujianoside can inhibit SA-β-gal activity and reduce p16 protein expression better than vitamin E.Low concentration of ciwujianoside inhibition in SA-β-gal activity less the effect of vitamin E.
(7) Cultured mouse thymocytes can be naturally occurring time-dependent apoptosis with the culture time period of the extension of S and G_2/M cells,a significant reduction in the proportion,decline in value-added.In the 20-100μmol/L ciwujianoside have cell intoxicity to cultured mouse thymocytes.Ciwujianoside can anti-aging by increasing index of thymus cells in mice,inhibition of apoptosis,which effect better than the vitamin E.20μmol/L ciwujianoside only inhibit apoptosis,no significant impact on value-added index,which effects no significant difference with vitamin E.
This study conclude that ciwujianoside have anti-aging effect,which is to achieve by enhancing antioxidant capacity and cellular immune function,reducing the expression of p16 protein,promoting thymocyte proliferation,inhibiting apoptosis of thymocytes.
本课题给成年SD大鼠连续腹腔注射D-半乳糖建立衰老动物模型后,利用不同浓度刺五加苷作用于该模型,以维生素E作为阳性对照,从机能和形态两个方面研究刺五加苷是否具有延缓衰老的作用。在得出刺五加苷具有延缓衰老作用的基础上,结合目前世界上比较公认的自由基、免疫、端粒长度、细胞凋亡衰老学说,从体内、外两个方面研究刺五加苷延缓衰老的机理。在体内,研究了刺五加苷对衰老大鼠抗氧化能力、免疫功能、p16蛋白和对衰老相关-β-半乳糖苷酶的影响;在体外,利用具有自发凋亡的胸腺细胞作为模型,观察了刺五加苷对小鼠胸腺细胞凋亡的作用。由于衰老过程涉及机体各个系统、不同结构层次,因此本研究在整体水平、组织器官水平、细胞水平以及分子水平,分别研究了刺五加苷延缓衰老的机制。
本研究的研究结果有以下几方面:
(1)D-半乳糖致衰老模型构建成功。模型大鼠组织中SOD、GSH-Px活性下降,iNOS活性升高,MDA、NO浓度升高,T淋巴细胞增殖功能下降,血清IL-2浓度下降,IL-6浓度和TNF-α浓度升高,组织SA-β-gal活性增强,p16蛋白表达增加。
(2)刺五加苷可以改善衰老大鼠功能。刺五加苷能增加衰老大鼠的胸腺指数和脑指数,增强学习和记忆能力,升高血中HDL-C浓度,降低TG、TC、LDL-C浓度,降低血液粘滞性。高浓度刺五加苷降低TG浓度、增强学习和记忆能力、增加胸腺和脑指数的作用好于维生素E,中、低浓度刺五加苷降低LDL-C作用效果弱于维生素E,低浓度刺五加苷改善大鼠学习和记忆能力作用也弱于维生素E。
(3)高浓度刺五加苷可以延缓卵巢组织形态衰老。刺五加苷作用后衰老大鼠卵泡细胞轮廓清,线粒体损伤减轻,核肿胀缓解,常染色质分布均匀,中、低浓度刺五加苷和维生素E作用后细胞器多种退行性改变仍很严重。
刺五加苷可延缓神经细胞退行性改变。高浓度刺五加苷可使神经细胞轮廓清晰,核膜完整光滑,常染色质分布均匀,但其对神经细胞质水肿、线粒体嵴损伤改善仍不明显,中、低浓度刺五加苷和维生素E作用后细胞器退行性改变较严重。
各浓度刺五加苷都可以抑制肝细胞退行性改变。刺五加苷可以使肝细胞轮廓清晰、线粒体形态基本完好,高浓度刺五加苷作用效果最好,胞质内可见大量粗面内质网呈板层状排列,线粒体丰富,糖原数量多。
(4)刺五加苷具有抗氧化作用。各浓度刺五加苷都可以升高衰老大鼠组织SOD、GSH-Px活性,抑制iNOS活性,降低MDA、NO浓度。高浓度刺五加苷提高GSH-Px、SOD活性、降低MDA和NO浓度、抑制iNOS活性的作用强于维生素E,中浓度提高GSH-Px活性、降低MDA浓度作用也强于维生素E,低浓度刺五加苷降低MDA和NO浓度作用弱于维生素E。
(5)刺五加苷具有延缓免疫衰老作用。中、高浓度刺五加苷都可以提高衰老大鼠T淋巴细胞增殖功能和IL-2浓度,降低IL-6浓度,高浓度还可以降低TNF-α浓度。高浓度刺五加苷提高T淋巴细胞增殖功能和IL-2浓度作用,降低IL-6和TNF-α浓度作用都强于维生素E;中浓度提高T淋巴细胞增殖功能和IL-2浓度作用也强于维生素E,低浓度刺五加苷调节机体细胞免疫功能的作用与维生素E比较差异不明显。
(6)刺五加苷具有抑制衰老相关-β-半乳糖苷酶活性和降低p16蛋白表达的作用。中、高浓度刺五加苷具有抑制大鼠衰老相关-β-半乳糖苷酶活性,降低组织p16蛋白表达的作用,低浓度只能抑制衰老相关-β-半乳糖苷酶活性。中、高浓度刺五加苷抑制组织衰老相关-β-半乳糖苷酶活性,降低组织p16蛋白表达作用强于维生素E;低浓度抑制组织SA-β-gal活性作用弱于维生素E。
(7)小鼠胸腺细胞随着培养时间延长,会发生时间依赖性凋亡,表现为S期和G_2/M期细胞比例减少,增值能力下降。50、100μmol/L刺五加苷可以增加胸腺小鼠细胞增值指数、抑制细胞凋亡,作用好于维生素E;20μmol/L刺五加苷能抑制细胞凋亡,作用效果与维生素E没有显著差异。
通过以上研究,本课题得出刺五加苷具有延缓机体衰老的作用,其作用机理与刺五加苷提高机体抗氧化能力、增强细胞免疫功能、降低p16蛋白表达、促进胸腺细胞增殖、抑制细胞凋亡相关。
Ciwujia containing a wide range of natural active ingredients,and non-toxic side effects, with the advantages of both temporary and permanent cures,people on the popular favor since ancient times.With the isolation and purification of bioactive substances in the development of technology,people have carried out a large number of active ingredients on the ciwujianoside and structural identification studies.Ciwujianoside is the use of modern means of extracting ciwujia from natural active substances.
In this study,by continuous subcutaneous injecting D-galactose to adult SD rats establish an animal model of aging,using of different concentrations ciwujianoside in rats,studying anti-aging from both functional and morphological.The result is ciwujianoside with anti-aging.Therefore,we research the current aging theory,such as the free radical theory,the immune theory of aging,telomere length theory,theory of apoptosis,study the mechanism of anti-aging ciwujianoside both in vitro and in vivo.
In vivo,the studied is carried out by ciwujianoside on antioxidant capacity,immune function,p16 protein and senescence-associated-β-galactosidase impact in aging rats.In vitro, the studied is carried out by the ciwujianoside on the role ofapoptosis in thymocytes,with the spontaneous apoptosis of thymocytes as a model.As the aging process involves various body systems,the study relate to the level of different structures,the mechanisms of ciwujianoside anti-aging of in the overall level,the level of tissues and organs,cells and molecular level.
The results of this study are the following:
(1) The D-gal-induced aging model do not change rat body weight,electrocardiogram, heart rate,WBC,RBC,HGB,PLT,MCV,ALT,AST,TP,ALB,GLO,not change in liver, heart,brain,spleen,kidney tissue vitality tNOS.However,it decrease SOD,GSH-Px activity, increase iNOS activity,MDA,NO concentration increase;T lymphocyte proliferation function,serum IL-2,IL-6 concentrations decrease,TNF-αconcentrations increase;tissue SA-β-gal activity and p16 protein expression enhance.
(2) Ciwujianoside can increase the rat thymus and brain aging index,and enhance learning and memory capacity,higher blood HDL-C concentration and lower TG,TC,LDL-C concentrations and lower blood viscosity,and high concentrati0ns of ciwujianoside obvious effect better than the low and middle.In addition,the high concentration of ciwujianoside reduct TG concentration,enhance learning and memory capacity,increase thymic index,and the role of the brain better than vitamin E.But effect of enhancing learning and memory capacity in the low concentration lower than that of the vitamin E.
(3) High concentrations of ciwujianoside follicle cells in aging rats could outline a clear and reduce the extent of mitochondrial injury,to alleviate the status of nuclear swelling,so that distribution euchromatin with delay ovarian aging patterns.However,in other concentrations of ciwujianoside and vitamin E,follicles occupy the cytoplasm is obvious edema in follicles,mitochondrial degeneration seen,a variety of cell degenerative changes are still very serious.In addition,high concentrations of ciwujianoside can make the outline of nerve cells in aging rats clear,smooth nuclear membrane integrity,euchromatin distribution, delay nerve cell degeneration,but the cytoplasm of nerve edema,mitochondrial cfistae damage does not improve significantly.
(4) Ciwujianoside can increase the SOD,GSH-Px activity,inhibiting iNOS activity and lower MDA,NO concentration.The role of high concentrations of ciwujianoside results significantly better than middle and low concentration groups,which is the role of a dose-dependent.High concentrations of ciwujianoside on increase T lymphocyte proliferation, IL-2 concentration,IL-6 concentrations,lower TNF-αconcentrations is better than the effect of vitamin E.Middle concentration ciwujianoside in aging rats only increase T lymphocyte proliferation and enhance IL-2 concentration better than vitamin E,The effect of low concentration ciwujianoside reducting MDA and NO concentration is lower than the vitamin E.
(5) Ciwujianoside to postpone the role of immunosenescence in a dose-dependent way.High concentrations of ciwujianoside can delaying immunosenescence by increasing T lymphocyte proliferation,IL-2 concentration,lowing IL-6 and TNF-αconcentrations.Middle concentrations of ciwujianoside increase T lymphocyte proliferation and IL-2 concentration better than vitamin E;Low concentration of ciwujianoside in the regulation of aging cellular immune function in rats is not obvious.High concentrations of ciwujianoside in aging rats increase T lymphocyte proliferation,IL-2 concentration,lower concentrations of IL-6 concentrations,TNF-αconcentrations effects are better than the vitamin E.Low concentration of ciwujianoside in the regulation cellular immune function compare with the vitamin E the difference is not obvious.
(6) Middle and high concentrations of ciwujianoside can inhibit SA-β-gal activity and lower p16 protein expression in a dose-dependent manner.Low concentrations of ciwujianoside only can inhibit SA-β-gal activity.The high and middle concentrations of ciwujianoside can inhibit SA-β-gal activity and reduce p16 protein expression better than vitamin E.Low concentration of ciwujianoside inhibition in SA-β-gal activity less the effect of vitamin E.
(7) Cultured mouse thymocytes can be naturally occurring time-dependent apoptosis with the culture time period of the extension of S and G_2/M cells,a significant reduction in the proportion,decline in value-added.In the 20-100μmol/L ciwujianoside have cell intoxicity to cultured mouse thymocytes.Ciwujianoside can anti-aging by increasing index of thymus cells in mice,inhibition of apoptosis,which effect better than the vitamin E.20μmol/L ciwujianoside only inhibit apoptosis,no significant impact on value-added index,which effects no significant difference with vitamin E.
This study conclude that ciwujianoside have anti-aging effect,which is to achieve by enhancing antioxidant capacity and cellular immune function,reducing the expression of p16 protein,promoting thymocyte proliferation,inhibiting apoptosis of thymocytes.
引文
1.曹广文,杜平,焦炳华,等.1992.枸杞子多糖、黄芪多糖、刺五加多糖和鼠伤寒杆菌内毒素多糖对LAK活性的调节作用[J].第二军医大学学报,13(3):206.
2.曹湘博,于乐洋,常雅萍.2007.D-半乳糖亚急性中毒拟衰老模型鼠免疫功能及生化指标变化的研究[J].中中国比较医学杂志,17(7):382-385.
3.陈海英,孔月红,蔡兆明.2005.健康大鼠衰老指标的增龄变化及形态学基础的相关性研究[J].山西医科大学学报,36(5):537-539.
4.陈貌连,宋风瑞,郭明全,等.2002.刺五加叶中黄酮类化合物的分析[J].分析化学,30(6):690-694.
5.陈貌连,宋凤瑞,郭明全,等.2002.刺五加叶中黄酮类化合物的结构鉴定[J].高等学校化学学报,23(5):805-808.
6.陈志宏,齐聪儒,高福禄,等.2004.天年饮对亚急性衰老大鼠睾丸组织SOD活性及生精细胞凋亡的影响[J].四川中医,22(8):11-12.
7.陈忠林,蔡宇.2005.刺五加多糖诱导S180肉瘤细胞凋亡和bax基因表达的影[J].中华实用中西医杂志,18(15):578-579.
8.淳于家龙,郭丽娜,张长顺.2002.无梗五加化学成分与药理活性的研究进展[J].中国药业,11(12),73-74.
9.党月兰,龚经纬.1998.红毛五加总昔的镇痛作用[J].中国药物依赖性杂志,7(2):88-92.
10.邸雅南,叶红军,王陆黎,等.2000.刺五加叶皂苷对肝癌细胞的影响[J].临床肝胆病杂志,6(2):104.
11.刁波,唐瑛,李德忠,等.2008.刺五加多糖对H_2O_2诱导海马细胞凋亡的保护作用[J].华南国防医学杂志,22(1):4-6.
12.董荔.1998.白介素-6和骨代谢:雌激素抗骨质疏松作用的分子机制[J].国外医学·老年医学分,19(3):127-130.
13.范少光,丁桂凤.1995.神经内分泌和免疫系统之间相互作用的介导物质[J].生理科学进展,26(2):175-183.
14.方允中,李文杰.1989.自由基与酶[M].北京:科学出版社,272.
15.风志慧,程时.1999.氧化型胆固醉与动脉粥样硬化的关系[J].生理科学进展,30(1):23-28.
16.高斌,高洪.2002.氧自由基与细胞损伤[J].动物医学进展,23(5):34-36.
17.高艳华,杨利敏,邢德刚,等.2002.刺五加叶皂甙对实验性Ⅱ型糖尿病大鼠血液流变学四个指标的 影响[J].黑龙江医药科学,25(2):8.
18.葛斌,许爱霞,杨社华.2004.黄芪多糖抗衰老作用机制的研究[J].中国医院药学杂志,24(10):610.
19.郭明全,宋风瑞,陈貌连,等.2002.超声提取.分光光度法测定刺五加叶中总皂苷含量[J].分析化学,30(2):250.
20.郭明全,宋凤瑞,陈貌连,等.2003.刺五加寡糖的电喷雾多级串联质谱研究[J].高等学校化学学报,24(9):1577-1581.
21.郭淑贞,张宗玉,童坦君.2003.衰老相关新基因CSIG的cDNA克隆和功能[J].中国生物化学与分子生物学报,19(5):612-617.
22.郭文晶,张守勤,吴华,等.2007.均匀设计优化高压提取刺五加叶中总黄酮[J].中药材,30(6):718-720.
23.郭英,蔡秀成,赵晓燕.1994.衰老与抗衰老纵横谈[J].医学与哲学,15(2):8-10.
24.韩晓琳,孙英,张宗玉,等.2004.P16降低二倍体成纤维细胞的凋亡敏感性[J].中国生物化学与分子生物学报,20(2):241-246.
25.郝群.2003.免疫系统衰老的研究进展[J].上海免疫学杂志,23(1):60-62.
26.贺立人.1999.刺五加注射液治疗重症肝炎26例效果观察[J].右江民族医学院学报,21(2):318.
27.黄德彬,冉瑞智,余昭芬.2004.刺五加注射对小鼠肿瘤坏因子的诱生作用[J]湖北民族学院学报(医学版),21(1)29-31.
28.黄力平,许豪文,曲镭,等.1998.维生素E和复方刺五加液对小白鼠疲劳性游泳运动的作用[J].中华物理医学杂志,20(2):84.
29.黄泰康.1994.常用中药成分与药理手册[M].北京:中国医药科技出版社,118.
30.黄英,杨龙,张宗玉,等.2001.人外周血淋巴细胞凋亡与年龄及p21WAF1的关系[J].中国生物化学与分子生物学报,17(1):124-127.
31.黄正明,杨新波,曹文斌,等.1998.CCl_4,D-Gal,ANIT对化学性肝损伤小鼠血液生化指标的影响[J].世界华人消化杂志,6(1):17-18.
32.惠宏襄,赵小宁,金明,等.1996.自由基与细胞凋亡[J].生物化学与生物物理进展,23(23):12-16.
33.减雪冰,胡怡秀.2002.天然维生素E延缓衰老作用的实验研究[J].实用预防医学,9(1):32-33.
34.江文,高华.1999.一氧化氮生物作用的双面性与缺血性脑损伤[J].卒中与神经疾病,6(1):63-64.
35.金义光,杜丽娜.2007.抗衰老研究:从基因到药物[N].中国医药报,08-06.
36.孔德娟,陈永春,李恩,等.1999.老年大鼠体内NO、NOS、AGEs和SOD水平与衰老的关系[J].中国老年学杂志,19(3):175-176.
37.孔祥峰,尹富贵,刘合军,等.2006.早期断奶仔猪生理生化参数和脏器指数的变化[J].中国实验动物学报,14(4):298-302.
38.李虹,白小涓,陈香美.2006.血管紧张素Ⅱ和NADPH氧化酶与血管衰老的相关性研究[J].中国老年学杂志,26(4):493-495.
39.李鸿鹄.2007.年龄再造.被忽视的衰老速度[M].第1版.上海:同济大学出版社,112-115.
40.李积胜,汪超,王静,等.2000.补锌对衰老大鼠睾丸细胞凋亡和一氧化氮合酶的影响[J].中国老年学杂志,20(2):93-94.
41.李宁川,祝瑾,金其贵.2000.刺五加制剂的人体抗疲劳实验研究[J].安徽体育科技,87(3):89.
42.李求实,王升旭.2002.刺五加总甙穴位贴敷抗睡眠剥夺作用的实验研究[J].华南国防医学杂志,20(5):317-320.
43.李筱玲,邓寒霜.2006.刺五加茎叶化学成分分析[J].商洛师范专科学校学报,20(1):103-105.
44.李艳芳,师树田,曹晓菁.2007.大鼠血清白细胞介素1β和肿瘤坏死因子α随增龄而变化[J].中华老年心脑血管病杂志,12(9):844-846.
45.李艳君,欧叶涛,李晓涛,等.2003.刺五加叶皂甙对Ⅱ型糖尿病大鼠GLP-1和血糖分泌的影响[J].解剖科学进展,9(3):238-239.
46.李宇,李建华,杨淑芳,等.2007.维生素E对慢性肾功能衰竭患者的微炎症和氧化应激状态的影响[J].第四局医大学学报,28(18),1666.
47.李占魁,安荣妹,陈惟昌,等.1996.人体组织超氧化物歧化酶的活性与年龄的关系[J].中日友好医院学报,10(3):208-211.
48.梁丽坚,蔡宇,梁少玲.2006.刺五加提取物抗肿瘤作用的实验研究[J].时珍国医国药,17(7):1187.
49.廖力夫,黎唯,王诚,等.2002.灰仓鼠重要内脏器官生长指数及其变化[J].兽类学报,22(4):299-304.
50.刘朝东,杨家树.2008.宁陕地区2517例血脂检测结果分析[J].实用医技杂志,15(22),2911-2912.
51.刘宏雁,李吉平,王秋晶,等.2000.刺五加叶皂苷对实验性高血脂症大鼠血小板形态的影响及其机理的初步探讨[J].人参研究,12(4):15-18.
52.刘起华,朱札,李文兰.1999.刺五加主要活性成分化学与药理研究[J].时珍国医国药,10(4):305.
53.刘晓瑞.2004.皮肤衰老的探讨[J].中国老年学杂志,24(1):82-83.
54.刘颖,凌昌全.1999.固真方对老龄大鼠免疫功能的调节作用[J].中国老年学杂志,19(2):104-105.
55.陆怡,潘华珍,许彩民.1996.氧化与细胞凋亡[J].生物化学与生理进展,23(2):118-121.
56.吕宝经,赵美华,黄国芳,等.1996.年龄变化与脂质过氧化损伤的分析[J].上海第二医科大学学 报,16(1):40-41.
57.吕晓英,李由,孙菊花,等.2001.红毛五加多糖诱导体外人胃癌细胞凋亡的研究[J].实用癌症杂志,146(1):6-8.
58.吕晓英,曾令福,王双印,等.2002.红毛五加多糖对体外人胃癌细胞的抑制作用及其作用机理[J].实用癌症杂志,15(3):243.
59.马东志.2003.维生素E对血液流变学的影响[J].河南医药信息,24(1),32-33.
60.马厚勋,曾凡荣,曾昭淳.1999.一氧化氮生物学作用及其与衰老的关系[J].国外医学老年医学分册,20(4):167-172.
61.马锐,柳星,伞宝君,等.2002.肿瘤化疗对细胞免疫系统的影响[J].中国实用内科杂志,22(6):352-353.
62.马秀英,党月兰.1999.红毛五加总苷对炎症性疼痛的镇痛作用[J].中药药理与临床,15(6):18-20.
63.潘竞锵,肖柳英,韩超,等.2004.葛根芩连汤拮抗D-半乳糖诱导大鼠糖耐量减退作用[J].广东药学,14(1):31-33.
64.潘力,崔丽等.2000.红景天素抗心肌老化的电镜观察和能谱分析[J].电子显微学报,19(3):307-308.
65.潘力,孙庆等.1996.红景天素抗大鼠大脑皮质老化作用的透射电镜观察[J].中华物理医学杂志,18(2):94-95.
66.钱小明,吴振国,施志明,等.1995.衰老小鼠组织牛磺酸含量与脂质过氧化损伤的关系[J].基础医学与临床,15(5):70.
67.邵迎红,母义明,李江源,等.2005.衰老大鼠睾丸间质细胞形态学观察[J].中国男科学杂志,19(2):10-12.
68.石学魁,王雅贤,周晓茵,等.2007.刺五加总黄酮对脑缺血大鼠脑组织P38及GAP-43蛋白表达影响的实验研究[J].中西医结合心脑血管病杂志,5(3):211-212.
69.睢大员,吕忠智,李淑惠,等.1994.刺五加叶皂苷降血糖作用[J].中国中药杂志,19(11):683-685.
70.睢大员,曲绍春,于小风,等.2004.刺五加叶皂苷对大鼠心肌缺血再灌注损伤的保护作用[J].中国中药杂志,29(1):71-74.
71.睢大员,于晓风,曲绍春,等.2005.刺五加叶皂苷对实验性脑缺血大鼠的保护作用[J].中草药,36(4):561-563.
72.唐兴文,董钮明,李春兰,等.2004.红毛五加总昔和多搪研究进展[J].兰州医学院学报,30(4):93-96.
73.陶明飞,杨卫东,王俊和.2004.刺五加对放射损伤骨髓微血管的保护作用[J].中国公共卫生,20(6):683-685.
74.佟丽,黄添友,梁谋,等.1994.刺五加多糖抗肿瘤作用与机理的实验研究[J].中国药理学通报,10(2):105-109.
75.佟丽,李吉采.1997.刺五加多糖研究进展[J].天然产物研究与开发,11(1):87.
76.童坦君,张宗玉主编.1995.医学老年学[M].北京:人民卫生出版社,12-16.
77.王柏昆,刑善田,周金黄.1990.枸杞多糖对小鼠T、杀伤T和NK细胞的免疫药理作用及对抗环磷酰胺的免疫抑制作用[J].中国药理学与毒理学杂志,4(1):39.
78.王柏欣,王淑湘,谭宏,等.2004.刺五加叶皂甙对糖尿病大鼠脂质过氧化物的作用[J].黑龙江医学科学,27(2):1-2.
79.王传社,李顺成,马治中,等.2000.血癖与衰老的实验研究回顾[J].中国中西医结合杂志,20(3):221.
80.王恩军,靳讳,王亚玲,等.2008.刺五加注射液对人宫颈癌细胞株Hela的细胞增殖有较强的抑制作用[J].河北北方学院学报,25(2),19-21.
81.王吉吉,赵新华,陆承荣,等.1999.D-半乳糖亚急性中毒大鼠拟衰老生理生化改变[J].实验动物科学与管理,16(2):24-25.
82.王瑾文,陈玻,周玫.1998.一氧化氮、超氧阴离子和过氧亚硝酸的作用和相互关系的研究进展[J].生命的化学,18(3):3-5.
83.王跃,付玉荣.2006.双歧杆菌脂磷酸抗免疫衰老的实验研究[J].中国免疫学杂志,22(3):200-202.
84.卫平.1988.短柄五加茎中氨基酸和金属元素分析[J].中药材,11(6):37.
85.温筱煦,程丽静,刘蔚,等.2006.刺五加总黄酮对小鼠红细胞膜流动性的影响[J].中国基层医药,13(8):1256-1257.
86.吴立军,阮丽军,郑健,等.1999.刺五加茎叶化学成分[J].药学学报,34(11):839.
87.吴伟康,罗汉川,侯灿.1994.增龄对小鼠心肌氧自由基浓度、超氧化物歧化酶活性及丙二醛含量的影响[J].中华老年医学,14(4):230-232.
88.吴永宁,王绪卿,李明,等.1997.刺五加制剂的人体抗疲劳试验与小鼠负重游泳试验的比较[J].中国食品卫生杂志,9(4):7.
89.吴永宁,王绪卿,赵立峰,等.1999.刺五加制剂对大学生恒定负荷下运动耐力的影响[J].中国校医,13(1):1-5.
90.谢蜀生,吕秀风,秦风华,等.1989.刺五加多糖免疫调节机理初探[J].中华微生物学和免疫学杂志,9(3):153-155.
91.邢有权,孙志忠,辛柏福.1991.刺五加果实挥发油成份的气相色谱-质谱分析[J].黑龙江大学自然科 学学报,8(4):87-90.
92.徐淑云,陈修.2002.药理实验方法学[M],第3版.北京:人民卫生出版社,1464-1472.
93.许爱霞,张振明,葛斌,等.2005.何首乌多糖对氧自由基及抗氧化酶活性的作用研究[J].中国药师,8(11):900-902.
94.许士凯.2000.当代抗衰老药物学研究的进展[J].药业纵横,9(11):19-21.
95.杨成吉.1990.多糖类及刺五加苷类的干扰索促诱生效应[J].中草药,21(1):27.
96.杨东丽,刘新文,童坦君,等.2002.年轻与衰老2BS细胞中差异表达基因片段的筛选及特征分析[J].中国生物化学与分子生物学报,18(4):456-460.
97.杨红英,李经才.2000.褪黑素对D-半乳糖衰老模型小鼠的作用[J].中国药理学通报,16(4):397-400.
98.杨吉成,徐鸿贞,刘静山.1988,刺五加多糖、羧甲基淀粉钠对S801和S7811细胞系促诱生干扰素的作用[J].中华微生物和免疫学杂志,4(5):329-330.
99.杨龙,黄英,张宗玉,等.1999.衰老与细胞凋亡[J].老年医学与保健,19(2):93-94.
100.杨扬,张义栋,姜吉文.2004.刺五加叶皂甙对GLP-1分泌影响的实验研究[J].福建中医药,35(3):38-41.
101.野岛武.1979.刺五加药理作用[J].汉方の临床(日),6:201.
102.叶红军,吴远,房家智,等.2002.刺五加皂甙对胃癌细胞膜电位和亚细胞结构的影响[J].中华消化杂志,22(1):48-49.
103.叶红军,邹兵,杜意平.2002.刺五加叶皂甙诱发肝癌细胞凋亡的研究[J].临床肝胆病杂志,18(3):162-163.
104.阴健,郭力弓.1993.刺五加-中药现代研究与临床应用[M].北京:学苑出版社,441-420.
105.余升红.2006.衰老与P16基因[J].中国优生与遗传杂志,14(9),3-4.
106.袁学千,王淑梅,高权国.2004.刺五加多糖增强鼠免疫功能的实验研究[J].中医药学报,32(4):48-49.
107.曾昭淳,马厚勋,曾繁荣.2000.不同年龄大鼠组织NO含量和NOS活性的变化与衰老之间的关系[J].中国老年学杂志,20(5):305-307.
108.战术,孙丰文,邵春杰,等.1996.刺五加叶皂苷单体SC3对培养大鼠心肌细胞自发性搏动及动作电位的影响[J].中国药学杂志,31(7):401-403.
109.张兵,侯家骥.1995.大鼠海马CA1区锥体神经元在衰老过程中的超微结构变化[J].神经解剖学杂志,11(3):249-251.
1l0.张东杰,冯昆,张爱武,等.2003.刺五加茶饮料抗疲劳作用的实验研究[J].营养学报,25(3):309.
111.张芳红,钟静芬,金家骅,等.1994.齐墩果酸在甘肃产八种五加科植物中的分布规律[J].中药材,17(9):29-31.
112.张敬一,杨惠敏,付琳杰,等.2001.刺五加多糖对小鼠Lewis肺癌的实验性干预作用研究[J].癌变畸变突变,13(4):270.
113.张莅霞,刘泓,董建平.1994.无梗红毛五加皮挥发油化学成分的研究[J].中国医学杂志,29(2):83-86.
114.张莅霞,刘淞.2001.红毛五加茎皮、叶及果实挥发油的GC-MS比较分析[J].中国中医基础科学杂志,7(5):24-27.
115.张曼颖,安继红,李昌辉.2002.刺五加叶皂甙诱导肺癌细胞凋亡的研究[J].吉林大学学报(医学版),28(1):37-39.
116.张松,王留兴,樊青霞,等.2007.刺五加叶皂苷联合冬凌草甲素对人食管癌Eca-109细胞的生长抑制作用[J].肿瘤基础与临床,20(3):226-229.
117.张熙,李文彬,张炳烈,等.1990.D-gal亚急性中毒大鼠拟衰老改变[J].中国药理学与毒理学杂志,4(4),309-310.
118.张玉华,韩丛成,曲绍春,等.2002.刺五加叶时大鼠实验性心肌梗死的保护作用[J].中国新药杂志,11(9):695-697.
119.赵俊霞,闰永鑫,赵娟,等.2008.刺五加多糖诱导人小细胞肺癌H446细胞凋亡[J].细胞生物学杂志,30(2):239-242.
120.赵余庆,柳江华.1989.刺五加中脂肪酸类和酯类成分的分离与鉴定[J].中医药学报,3:55-57.
121.郑春英,刘松梅,李宏涛,等.2007.胶束电动毛细管电泳同时检测刺五加中紫丁香苷及绿原酸的含量[J].中国药学杂忠,42(16):1248-1251.
122.郑丽杰,钱东华,戴洪龄.1994.红细胞膜的脂质过氧化物与衰老[J].白求恩医科大学学报,20(1):20-21.
123.郑日男,金海艳,裴风郁.1998.刺五加对胃缺血再灌注损伤防护作用的实验研究[J].中国中西医结合脾胃杂志,6(4):226-228.
124.郑荣梁.1992.衰老的自由基学说[J].实用老年医学,6(1):31-33.
125.周逸,唐其柱,史锡滕,等.2005.刺五加叶皂甙预处理对供心保存的实验研究[J].中国微循环,9(1):30-32.
126.邹承鲁主编.2000.当代生物学[M].北京:中国致公出版社,394-396.
127.Robert Goldman Ronald Klatz.2005.抗衰老革命[M].沈阳:辽宁科技出版社,10-11.
128.Adamas CS,Horron WE JR.1998.Chondrocyte Apoptosislncreases with Age in the Articular Catilage of AdultAnimals[J].Anat Rec,250(4):418-425.
129.Albina JE,Abate JA,Henry WL,et al.1991.Nitric oxide production is required for murine resident peritoneal macrophages to suppress mitogen-stimulated T cell proliferation.Role of IFN-gamma in the induction of the nitric oxide-synthesizing pathway[J].J Immunol,147(1):144-148.
130.Aleorta DA,XiongY.1996.Invovement of the cyclin-dependent kinaseinhibitorp 16~((INK4a)) in replicative seneseence of normal human fibroblasts[J].Proc Nad Sead Sci USA,93(24):13742-13747.
131.Allan LG,Arabinda G,Marion MZ,et al.1972.Purification and Biological Activity of Thymosin,a Hormone of the Thymus Gland[J].Proc Natl Acad Sci U S A,69(7):1800-1803.
132.Anna VM,Shalom GS,Nancy MJ,et al.2006.Increasing p16~(INK4a) expression decreases forebrain progenitors and neurogenesis during ageing[J].Nature,443(28),448-452.
133.Baker SJ,Reddy P.1996.Transducers of life and death:TNF receptor superfaraily and associated proteins[J].Oncogene,12( 1 ):21-29.
134.Beckman JS,Beckman TW,Chen J,et al.1990.Apparent Hydroxyl Radical Production by Peroxynitrite:Implications for Endothelial Injury from Nitric Oxide and Superoxide[J].Proc Natl Acad Sci USA,87(9):1620-1624.
135.Biesalski HK.2002.Free radical theory of aging[J].Curr Opin Clin Nutr Metab Care,5(1):5-10.
136.Bodey B.Bodey B.Siegel S E,et al.1999.MoIecular Biological Ontogenes is of the Thymic Ticulo-epithelial Cell Network during the Organization of the Cellular Microenvironment[J].In vivo (Athens,Greece) ,13(3):267-294.
137.Bodnar AG,Ouellette M,Frolkis M,et al.1998.Extension of life-span by introduction of telomerase into normal human cells[J].Science,279(5349):349-352.
138.Bruunsggaard H,Pederson AN,SchrollM,et al.1999.Impaired production of proinflammatory cytokines in resonse to lopopolysaccharides(LPS) stimu-lation in elderly humans[J].Clin Exp Immunol,118(2):235-241.
139.Cao SX.Dhahbi JM.Mote PL,et al.2001.Genomic profiling of short and long-term caloric restriction effects in the liver of aging mice[J].Proc Natl Acad Sci U S A,98( 19):10630-10635.
140.Cristofalo VJ.Volker C.Francis MK,et al.1998.Age-dependent modifications of gene expression in human fibroblasts[J].Crit Rev Eukaryot Gene Expr,8(1):43-80.
141.Das N,Levine RL,Orr WC,et al.2001 .Selectivity of protein oxidative damage aging in Drosophila melanogaster[J].Biochem J,360(1):209-216.
142.Dawson VL,Dawson TM.Bartley DA,et al.1993.Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures[J].J Neurosci Jun,13(6):2651 2651-2661.
143.Dimiri GP,Lee X,Basile G,et al.I995.A biomarker that identifies senescent human cells in culture and in aging skin in vivo[J].Proc Natl Acad Sci USA,92(20):9363-9367.
144.Dowdy SF.Hinds PW.Louie K,et a 1.1993.Physical interaction of the retinoblastoma protein with human D cyclins[J].Cell,73(7):499-511.
145.Egashira K,Inou T,HirookaY,et al.1993.Effects of age on endothelium_dependent vasodilation of resistance coronary artery by acetylukoline in humans[J].Cireulation,88(1):77-81.
146.Elisabeth B,Sylvie G,Denis M,et al.1999.Alterations of Rb Pathway (Rb-p16~(INK4)-Cyclin D1) in Preinvasive Bronchial Lesions[J].Clinical Cancer Research,5(2):243-250.
147.Fahn S,Cohen G.1992.The oxidative stress hypothesis in parkinsons disease:evedenee supporting it[J].Ann Neurol,32(6):804-812.
148.Ferrini M,Magee TR,Vernet D,et a 1.2001.Aging-related expression of inducible nitric oxide synthase and markers of tissue damage in the rat penis[J].Biol Reprod,64(3):974-982.
149.Franceschi C,Monti D.Sansoni P,et al.1995.The immunology of exceptional individuals:the lesson of centenarians[J].Immunol Today,16( 1):12-16.
150.Gentiloni SN.Mazzonc M,Portale C,et al.2001.Nitric oxide:ageneral review about the different roles of this innocent radial[J].Minerva Med,92(3):167-171.
151.Gerhard M,Roddy MA.Creager SJ,et al.1996.Aging progressively impair Sendothelium-dependent vasodilation in forearm resistance vessels of humans[J].Hypertension,27(4):849-853.
152.Giardino R,Giavaresi G,Fini M,et al.2002.The role of different chemical modifications of superoxide dismutase in preventing a prolonged muscular is chemislreperfusion injury[J].Artif Cells Blood Immubiol Biotechmol,30(3):189-198.
153.Ginaldi L,De Martinis M,D'Ostilio A,et al.1999.The immune system in the elderly Ⅲ Innate immunity[J].Immunol Res,20(2):117-126.
154.Ginaldi L.Loreto MF.Comi MP,et al.2001.Immunosenescence and infectious diseases[J].Microbes Infect,3(10):851-857.
155.Gorczynski RM.Cindar B,Ramakrishna V,et al.1997.An antibody specific for interleukin-6 reverse age associated changes in spontaneous and induced cytokine production in mice [J].Immunology,92(1):20-25.
156.Gunnar Skarping,Marianne Dalene.1995.Determination of 4,4-methylenediphenyldianiline(MDA) and identification of isomers in technical-grade MDA in hydrolysed plasma and urine from workers esposed to methylene diphenyl diisocyanate by gas chromatograp-hy-mass soectrometry[J].Journal of Chromatography B,663(2):209-216.
157.Hannun YA.Luberto C.2000.Ceramide in the eukaryotic stress response[J].Trends Cell Biol.10 (2):73-80.
158.Harman D.1981.The aging process[J].Proc Natl Acad Sci USA,78(11):7124-7128.
159.Hashimoto S,Oehs RL.1998.Chondrocyte-derived ApoptoticBodies and Calcification of Articular Cartilage[J].Proc Natl Acad Sci USA,95(6):3094-3095.
160.Hinds PW.Mittnacht S,Dulic V,et al.1992.Regulation of retinoblastoma protein functions by ectopic expression of human cyclins[J].Cell,70(6):993-1006.
161.Ian'kova Vl,Ivanova IL.2003 .Age-related changes of lipids pectrum.level of lipid peroxidation,and antioxidant defence in the liver and blood of rats[J].Ross Fiziol Zh Im I M Seehenova,89(7):828-836.
162.Johan Bjorksten,William J.Champion.1942.Mechanical Influence upon Tanning[J].Am.Chem.Soc,64 (4),868-869.
163.John DM .Jianguo W,Tong Z,et al.1997.Cell death and longevity amplications of Fas - mediated apoptosis in T cell senescence [J].Immunol Rev,160 (1):19-25.
164.Jorge D.Erusalimsky DJ.Kurz.2005.Cellular senescence in vivorlts relevance in ageing and cardiovascular disease[J].Exp Gerontol,40(2):634-642.
165.Krishnamurthy J,Ramsey MR,Ligon KL,et al.2006.p16~(INK4a) induces an age-dependent decline in islet regenerative potential[J].Nature,443(7110):453-457.
166.Krishnaraj R.1997.Senescence and cytokines modulate the NK cell expression[J].Mech Aging Dev,96(1-3):89-101.
167.Kuo J,HC Yang,IS Cheng,et al.2005.Supplementation of eleutherococcus senticosus (CIWUJIA) on anti-fatigue function in human.The 18th International Congress of Nutrition in South Africa[C],11,19-23.
168.L.Hayflick,Moorehead PS.1961.The serial cultivation of human diploid cell strains[J].Exp Cell Res,25(12),585-621.
169.Lee CK,Klopp RQWeindruch R,et al.1999.Gene expression profile of aging and its retardation by caloric restriction[J].Gelence,285(5432):1390-1393.
170.Lin HZ,Yang SQ.Chukaree C,et al.2000.Meformin fatty liver disease in obese,leptin deficient mice[J].Nat Med,6(9),998-1003.
171.Luo Y,Umegaki H.Dopamine Induces Apoptosis.1998.Through an Oxidation Involved SAPK / JNK Activation Pathway[J].J Biol Chem,273(6):3756-3764.
172.Manolagas S C.Cellular and Molecular.1998.Mechanisms of Osteporosis[J].Aging,10(3):182-190.
173.Martin SJ,Green DR,Cotter TG1994.Dicing with death:dissecting the components of the apoptosis machinery[J].Trends Biochem Sci Jan,19(1):26-30.
174.Masoro EJ.1998.Hormesis and the antiaging action of dietary restriction[J].Exp Gerontol,33 (1-2):61-66.
175.Morreau H,Galjart NJ,Gillemans N,et al.1989.Alternative spli_cing of beta_galactosidase mRNA generates the classic lysosomal enzyme and a beta_galactosidase_related protein[J].J Biol Chem,264(34):20655-20663.
176.Norrback KF,Enblad G,Erlanson M,et al.1998.Telomerase activity in Hodgkin a disease[J].Blood,92 (2):567-574.
177.Orgel LE.1963.The maintenance of the accuracy of protein synthesis and its relevance to aging[J].Proc Nat Acad Sci USA,49(4):517-521.
178.Park SY.Chang SY.Yook CS.et al.2000.New3,4-seco-lu-pane-type triterpene glycosides from Acanthopanax senticosus forma inermis[J].J Nat Prod,63(12):1630-1633.
179.Parker RJ,Berkowitz BA,Lee CH,et al.1978.Vascular relaxation,aging and thyroid hormones[J].Mech Ageing Dev,8(6):397-405.
180.Pendergrass WR ,Lane MA ,Bodkin NL,et al.1999.Cellular proliferation potential during aging and caloric restration in rhesus monkeys[J].J cell Phsiol,180(2):123-130.
181.Pinkston-Gosse J.Kenyon C.2007.DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans Nature Genetics[J].Nat Genet,39(11):1403-1409.
182.Pratieo D.2002.Lipid peroxidation and the aging process[J].Sei Aging Knowledge Environ,2002(50):5-9.
183.Prolla TA.2002.DNA microarray analysis of the aging brain[J].Chem Senses,27(3):299-306.
184.Rider DA.Sinclair AJ,Young SP,et a 1.2003.Oxidative inactivation of CD45 protein tyrosine phosphatase may contribute to T lymphocyte dysfunction in the elderly [J].Mech Ageing Dev,124:191-198.
185.Rusting,R.L.1992.Trends in biology.Why do we age[J]?Sci Am,267(6):130-141.
186.Sandhu C,Donovan J.Bhattacharya N,et al.2000.Reduction of Cdc25A contributes to cyclin El-Cdk2 inhibition at senescence in human mammary epithelial cells[J].Oncogene,19(47):5314-5323.
187.Sandhu SK,Kaur G2002.Alterations in oxidative stress scavenger system in aging rat brain and lumphocytes[J].Biogerontology,3(3):161 -173.
188.Sarkar G,Bolander ME.1995.Telomeres,telomerase,and cancer[J].Science,268 (5214):1115-1117.
189.Segre D,Miller RA,Abraham GN.et al.1989.Aging and the Immune system.J Gerontol,44(6):164-168.
190.Shan BE.Yoshita Y.Sugiura T ,et al.1999.Suppressive effect of Chinese medicinal herb,Acanthopanax gracilistylus,extract oil human lymphocytes in vitro[J].Clinical & Experimental Immunology,118(1):41-48.
191.Shao CJ.Ryoji K,Xu J D,et al.1989.Saponins from Leaves of Acanthopanax Senticosus Harms,CiwujiaII.Structures of Ciwujia nosides B,Al,A2,A3,A4andD3[J].Chem Pharm Bull,37(1):42-46.
192.Shelton DN ,Chang E.Whittier PS,et al.1999.Microarray analysis of replicative senescence.[J]Current biology,9( 17):939-945
193.Shi X,Dai C,Nuttall AL.2003.Altered expression of inducible nitric oxide synthase(iNOS)in the cochlea[J].Hear Res,177( 1 -2):43-52.
194.Siles E.Martinez-Lara E,CafihueIo A,et al.2002.Age-related changes of the nitric oxide system in the rat brain[J].Brain Res,956(2):385-392.
195.Sohal RS,Ku HH,Agarwal S,et al.1994.0xidative damage,mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse[J].Mech.Ageing Dev,74(1-2):121-133.
196.Song X,Bao M,Li D,and YM Li.1999.Advanced glycation in D-galactose induced mouse aging model[J].Mech Ageing Dev,108(3):239-251.
197.Stein GH,Beeson M.Gordon L.1990.Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts[J].Science,249(4969):666-669.
198.Stephen Bachows Ki.Yong Xu,Donald ES,et al.1998.Role of Oxidative Stress in the Selective Toxicity of Dieldrin in the Mouse Liver[J].Toxicology and Applied Pharmacology,150(2):301-309.
199.Tahira F and Akhlaq A.2008.Aging:an important factor for the pathogenesis of neurodegenerative diseases[J].Mechanisms of Ageing and Development,130(4):203-215.
200.Titia de Lange.1998.Telomeres and senescence:ending the debate[J].Science,279(3):334-335.
201.van Dam MJ,de Groot E,clee sM,et al .2002.Association between increased arterial-wall thickness and impairment in ABCAl-driven cholesterol efflux:an observational study[J].Lancet,359(9300):37-4 2.
202.Venable ME,Lee JY,Smyth MJ,et al.1995.Role of ceramide in cellular senescenee[J].J Biol Chem,270(51 ):30701-30708.
203.Wang E,Lacelle C,Xu S,et al.2002.Designer microarrays:from soup to nuts[J].J Gerontol A Biol Sci Med Sci,57(11):B400-B405.
204.Warner HR,Hodes R,Pocinki K.1997.What does cell death have to do with aging [J]?J Am Geriatr Soc,45(9):1140-1146.
205.Weindruch R,Kayo T,Lee CK,et al.2001.Microarray profiling of gene expression in aging and its alteration by caloric restriction in mice[J].J Nutr,131(3):918S-923S.
206.Weksler ME.2000.Changes in the B-cell repertoire with age[J].Vaccine,18(16):1624-1628.
207.Weng NP.2006.Ageing of the immune system:how much can the adaptive immune system adapt[J].Immunity,24(5):495.
208.Yang FF.Yuan SG,Yew DT.2008.Use of functional magnetic resonance imaging (blood oxygenation level-dependent imaging,diffusion tensor imaging and magnetic resonance spectroscopy) in brain development research.Neuroembryol aging,5(8):56-59
209.Zaciragic A,Nakasicindic E,Hadzovic A,et al.2004 .Average values of electrocardiograph parameters in healthy,adult Wistar rats[J].Med Arh,58(5):268-270.
210.Zissel G,Schlaak M,Muler-Quemheim J.1999.Age.related decrease in accessory cell function of hunmn alveolar macrophages[J].J Invest Med,47(1 ):51-56.
2.曹湘博,于乐洋,常雅萍.2007.D-半乳糖亚急性中毒拟衰老模型鼠免疫功能及生化指标变化的研究[J].中中国比较医学杂志,17(7):382-385.
3.陈海英,孔月红,蔡兆明.2005.健康大鼠衰老指标的增龄变化及形态学基础的相关性研究[J].山西医科大学学报,36(5):537-539.
4.陈貌连,宋风瑞,郭明全,等.2002.刺五加叶中黄酮类化合物的分析[J].分析化学,30(6):690-694.
5.陈貌连,宋凤瑞,郭明全,等.2002.刺五加叶中黄酮类化合物的结构鉴定[J].高等学校化学学报,23(5):805-808.
6.陈志宏,齐聪儒,高福禄,等.2004.天年饮对亚急性衰老大鼠睾丸组织SOD活性及生精细胞凋亡的影响[J].四川中医,22(8):11-12.
7.陈忠林,蔡宇.2005.刺五加多糖诱导S180肉瘤细胞凋亡和bax基因表达的影[J].中华实用中西医杂志,18(15):578-579.
8.淳于家龙,郭丽娜,张长顺.2002.无梗五加化学成分与药理活性的研究进展[J].中国药业,11(12),73-74.
9.党月兰,龚经纬.1998.红毛五加总昔的镇痛作用[J].中国药物依赖性杂志,7(2):88-92.
10.邸雅南,叶红军,王陆黎,等.2000.刺五加叶皂苷对肝癌细胞的影响[J].临床肝胆病杂志,6(2):104.
11.刁波,唐瑛,李德忠,等.2008.刺五加多糖对H_2O_2诱导海马细胞凋亡的保护作用[J].华南国防医学杂志,22(1):4-6.
12.董荔.1998.白介素-6和骨代谢:雌激素抗骨质疏松作用的分子机制[J].国外医学·老年医学分,19(3):127-130.
13.范少光,丁桂凤.1995.神经内分泌和免疫系统之间相互作用的介导物质[J].生理科学进展,26(2):175-183.
14.方允中,李文杰.1989.自由基与酶[M].北京:科学出版社,272.
15.风志慧,程时.1999.氧化型胆固醉与动脉粥样硬化的关系[J].生理科学进展,30(1):23-28.
16.高斌,高洪.2002.氧自由基与细胞损伤[J].动物医学进展,23(5):34-36.
17.高艳华,杨利敏,邢德刚,等.2002.刺五加叶皂甙对实验性Ⅱ型糖尿病大鼠血液流变学四个指标的 影响[J].黑龙江医药科学,25(2):8.
18.葛斌,许爱霞,杨社华.2004.黄芪多糖抗衰老作用机制的研究[J].中国医院药学杂志,24(10):610.
19.郭明全,宋风瑞,陈貌连,等.2002.超声提取.分光光度法测定刺五加叶中总皂苷含量[J].分析化学,30(2):250.
20.郭明全,宋凤瑞,陈貌连,等.2003.刺五加寡糖的电喷雾多级串联质谱研究[J].高等学校化学学报,24(9):1577-1581.
21.郭淑贞,张宗玉,童坦君.2003.衰老相关新基因CSIG的cDNA克隆和功能[J].中国生物化学与分子生物学报,19(5):612-617.
22.郭文晶,张守勤,吴华,等.2007.均匀设计优化高压提取刺五加叶中总黄酮[J].中药材,30(6):718-720.
23.郭英,蔡秀成,赵晓燕.1994.衰老与抗衰老纵横谈[J].医学与哲学,15(2):8-10.
24.韩晓琳,孙英,张宗玉,等.2004.P16降低二倍体成纤维细胞的凋亡敏感性[J].中国生物化学与分子生物学报,20(2):241-246.
25.郝群.2003.免疫系统衰老的研究进展[J].上海免疫学杂志,23(1):60-62.
26.贺立人.1999.刺五加注射液治疗重症肝炎26例效果观察[J].右江民族医学院学报,21(2):318.
27.黄德彬,冉瑞智,余昭芬.2004.刺五加注射对小鼠肿瘤坏因子的诱生作用[J]湖北民族学院学报(医学版),21(1)29-31.
28.黄力平,许豪文,曲镭,等.1998.维生素E和复方刺五加液对小白鼠疲劳性游泳运动的作用[J].中华物理医学杂志,20(2):84.
29.黄泰康.1994.常用中药成分与药理手册[M].北京:中国医药科技出版社,118.
30.黄英,杨龙,张宗玉,等.2001.人外周血淋巴细胞凋亡与年龄及p21WAF1的关系[J].中国生物化学与分子生物学报,17(1):124-127.
31.黄正明,杨新波,曹文斌,等.1998.CCl_4,D-Gal,ANIT对化学性肝损伤小鼠血液生化指标的影响[J].世界华人消化杂志,6(1):17-18.
32.惠宏襄,赵小宁,金明,等.1996.自由基与细胞凋亡[J].生物化学与生物物理进展,23(23):12-16.
33.减雪冰,胡怡秀.2002.天然维生素E延缓衰老作用的实验研究[J].实用预防医学,9(1):32-33.
34.江文,高华.1999.一氧化氮生物作用的双面性与缺血性脑损伤[J].卒中与神经疾病,6(1):63-64.
35.金义光,杜丽娜.2007.抗衰老研究:从基因到药物[N].中国医药报,08-06.
36.孔德娟,陈永春,李恩,等.1999.老年大鼠体内NO、NOS、AGEs和SOD水平与衰老的关系[J].中国老年学杂志,19(3):175-176.
37.孔祥峰,尹富贵,刘合军,等.2006.早期断奶仔猪生理生化参数和脏器指数的变化[J].中国实验动物学报,14(4):298-302.
38.李虹,白小涓,陈香美.2006.血管紧张素Ⅱ和NADPH氧化酶与血管衰老的相关性研究[J].中国老年学杂志,26(4):493-495.
39.李鸿鹄.2007.年龄再造.被忽视的衰老速度[M].第1版.上海:同济大学出版社,112-115.
40.李积胜,汪超,王静,等.2000.补锌对衰老大鼠睾丸细胞凋亡和一氧化氮合酶的影响[J].中国老年学杂志,20(2):93-94.
41.李宁川,祝瑾,金其贵.2000.刺五加制剂的人体抗疲劳实验研究[J].安徽体育科技,87(3):89.
42.李求实,王升旭.2002.刺五加总甙穴位贴敷抗睡眠剥夺作用的实验研究[J].华南国防医学杂志,20(5):317-320.
43.李筱玲,邓寒霜.2006.刺五加茎叶化学成分分析[J].商洛师范专科学校学报,20(1):103-105.
44.李艳芳,师树田,曹晓菁.2007.大鼠血清白细胞介素1β和肿瘤坏死因子α随增龄而变化[J].中华老年心脑血管病杂志,12(9):844-846.
45.李艳君,欧叶涛,李晓涛,等.2003.刺五加叶皂甙对Ⅱ型糖尿病大鼠GLP-1和血糖分泌的影响[J].解剖科学进展,9(3):238-239.
46.李宇,李建华,杨淑芳,等.2007.维生素E对慢性肾功能衰竭患者的微炎症和氧化应激状态的影响[J].第四局医大学学报,28(18),1666.
47.李占魁,安荣妹,陈惟昌,等.1996.人体组织超氧化物歧化酶的活性与年龄的关系[J].中日友好医院学报,10(3):208-211.
48.梁丽坚,蔡宇,梁少玲.2006.刺五加提取物抗肿瘤作用的实验研究[J].时珍国医国药,17(7):1187.
49.廖力夫,黎唯,王诚,等.2002.灰仓鼠重要内脏器官生长指数及其变化[J].兽类学报,22(4):299-304.
50.刘朝东,杨家树.2008.宁陕地区2517例血脂检测结果分析[J].实用医技杂志,15(22),2911-2912.
51.刘宏雁,李吉平,王秋晶,等.2000.刺五加叶皂苷对实验性高血脂症大鼠血小板形态的影响及其机理的初步探讨[J].人参研究,12(4):15-18.
52.刘起华,朱札,李文兰.1999.刺五加主要活性成分化学与药理研究[J].时珍国医国药,10(4):305.
53.刘晓瑞.2004.皮肤衰老的探讨[J].中国老年学杂志,24(1):82-83.
54.刘颖,凌昌全.1999.固真方对老龄大鼠免疫功能的调节作用[J].中国老年学杂志,19(2):104-105.
55.陆怡,潘华珍,许彩民.1996.氧化与细胞凋亡[J].生物化学与生理进展,23(2):118-121.
56.吕宝经,赵美华,黄国芳,等.1996.年龄变化与脂质过氧化损伤的分析[J].上海第二医科大学学 报,16(1):40-41.
57.吕晓英,李由,孙菊花,等.2001.红毛五加多糖诱导体外人胃癌细胞凋亡的研究[J].实用癌症杂志,146(1):6-8.
58.吕晓英,曾令福,王双印,等.2002.红毛五加多糖对体外人胃癌细胞的抑制作用及其作用机理[J].实用癌症杂志,15(3):243.
59.马东志.2003.维生素E对血液流变学的影响[J].河南医药信息,24(1),32-33.
60.马厚勋,曾凡荣,曾昭淳.1999.一氧化氮生物学作用及其与衰老的关系[J].国外医学老年医学分册,20(4):167-172.
61.马锐,柳星,伞宝君,等.2002.肿瘤化疗对细胞免疫系统的影响[J].中国实用内科杂志,22(6):352-353.
62.马秀英,党月兰.1999.红毛五加总苷对炎症性疼痛的镇痛作用[J].中药药理与临床,15(6):18-20.
63.潘竞锵,肖柳英,韩超,等.2004.葛根芩连汤拮抗D-半乳糖诱导大鼠糖耐量减退作用[J].广东药学,14(1):31-33.
64.潘力,崔丽等.2000.红景天素抗心肌老化的电镜观察和能谱分析[J].电子显微学报,19(3):307-308.
65.潘力,孙庆等.1996.红景天素抗大鼠大脑皮质老化作用的透射电镜观察[J].中华物理医学杂志,18(2):94-95.
66.钱小明,吴振国,施志明,等.1995.衰老小鼠组织牛磺酸含量与脂质过氧化损伤的关系[J].基础医学与临床,15(5):70.
67.邵迎红,母义明,李江源,等.2005.衰老大鼠睾丸间质细胞形态学观察[J].中国男科学杂志,19(2):10-12.
68.石学魁,王雅贤,周晓茵,等.2007.刺五加总黄酮对脑缺血大鼠脑组织P38及GAP-43蛋白表达影响的实验研究[J].中西医结合心脑血管病杂志,5(3):211-212.
69.睢大员,吕忠智,李淑惠,等.1994.刺五加叶皂苷降血糖作用[J].中国中药杂志,19(11):683-685.
70.睢大员,曲绍春,于小风,等.2004.刺五加叶皂苷对大鼠心肌缺血再灌注损伤的保护作用[J].中国中药杂志,29(1):71-74.
71.睢大员,于晓风,曲绍春,等.2005.刺五加叶皂苷对实验性脑缺血大鼠的保护作用[J].中草药,36(4):561-563.
72.唐兴文,董钮明,李春兰,等.2004.红毛五加总昔和多搪研究进展[J].兰州医学院学报,30(4):93-96.
73.陶明飞,杨卫东,王俊和.2004.刺五加对放射损伤骨髓微血管的保护作用[J].中国公共卫生,20(6):683-685.
74.佟丽,黄添友,梁谋,等.1994.刺五加多糖抗肿瘤作用与机理的实验研究[J].中国药理学通报,10(2):105-109.
75.佟丽,李吉采.1997.刺五加多糖研究进展[J].天然产物研究与开发,11(1):87.
76.童坦君,张宗玉主编.1995.医学老年学[M].北京:人民卫生出版社,12-16.
77.王柏昆,刑善田,周金黄.1990.枸杞多糖对小鼠T、杀伤T和NK细胞的免疫药理作用及对抗环磷酰胺的免疫抑制作用[J].中国药理学与毒理学杂志,4(1):39.
78.王柏欣,王淑湘,谭宏,等.2004.刺五加叶皂甙对糖尿病大鼠脂质过氧化物的作用[J].黑龙江医学科学,27(2):1-2.
79.王传社,李顺成,马治中,等.2000.血癖与衰老的实验研究回顾[J].中国中西医结合杂志,20(3):221.
80.王恩军,靳讳,王亚玲,等.2008.刺五加注射液对人宫颈癌细胞株Hela的细胞增殖有较强的抑制作用[J].河北北方学院学报,25(2),19-21.
81.王吉吉,赵新华,陆承荣,等.1999.D-半乳糖亚急性中毒大鼠拟衰老生理生化改变[J].实验动物科学与管理,16(2):24-25.
82.王瑾文,陈玻,周玫.1998.一氧化氮、超氧阴离子和过氧亚硝酸的作用和相互关系的研究进展[J].生命的化学,18(3):3-5.
83.王跃,付玉荣.2006.双歧杆菌脂磷酸抗免疫衰老的实验研究[J].中国免疫学杂志,22(3):200-202.
84.卫平.1988.短柄五加茎中氨基酸和金属元素分析[J].中药材,11(6):37.
85.温筱煦,程丽静,刘蔚,等.2006.刺五加总黄酮对小鼠红细胞膜流动性的影响[J].中国基层医药,13(8):1256-1257.
86.吴立军,阮丽军,郑健,等.1999.刺五加茎叶化学成分[J].药学学报,34(11):839.
87.吴伟康,罗汉川,侯灿.1994.增龄对小鼠心肌氧自由基浓度、超氧化物歧化酶活性及丙二醛含量的影响[J].中华老年医学,14(4):230-232.
88.吴永宁,王绪卿,李明,等.1997.刺五加制剂的人体抗疲劳试验与小鼠负重游泳试验的比较[J].中国食品卫生杂志,9(4):7.
89.吴永宁,王绪卿,赵立峰,等.1999.刺五加制剂对大学生恒定负荷下运动耐力的影响[J].中国校医,13(1):1-5.
90.谢蜀生,吕秀风,秦风华,等.1989.刺五加多糖免疫调节机理初探[J].中华微生物学和免疫学杂志,9(3):153-155.
91.邢有权,孙志忠,辛柏福.1991.刺五加果实挥发油成份的气相色谱-质谱分析[J].黑龙江大学自然科 学学报,8(4):87-90.
92.徐淑云,陈修.2002.药理实验方法学[M],第3版.北京:人民卫生出版社,1464-1472.
93.许爱霞,张振明,葛斌,等.2005.何首乌多糖对氧自由基及抗氧化酶活性的作用研究[J].中国药师,8(11):900-902.
94.许士凯.2000.当代抗衰老药物学研究的进展[J].药业纵横,9(11):19-21.
95.杨成吉.1990.多糖类及刺五加苷类的干扰索促诱生效应[J].中草药,21(1):27.
96.杨东丽,刘新文,童坦君,等.2002.年轻与衰老2BS细胞中差异表达基因片段的筛选及特征分析[J].中国生物化学与分子生物学报,18(4):456-460.
97.杨红英,李经才.2000.褪黑素对D-半乳糖衰老模型小鼠的作用[J].中国药理学通报,16(4):397-400.
98.杨吉成,徐鸿贞,刘静山.1988,刺五加多糖、羧甲基淀粉钠对S801和S7811细胞系促诱生干扰素的作用[J].中华微生物和免疫学杂志,4(5):329-330.
99.杨龙,黄英,张宗玉,等.1999.衰老与细胞凋亡[J].老年医学与保健,19(2):93-94.
100.杨扬,张义栋,姜吉文.2004.刺五加叶皂甙对GLP-1分泌影响的实验研究[J].福建中医药,35(3):38-41.
101.野岛武.1979.刺五加药理作用[J].汉方の临床(日),6:201.
102.叶红军,吴远,房家智,等.2002.刺五加皂甙对胃癌细胞膜电位和亚细胞结构的影响[J].中华消化杂志,22(1):48-49.
103.叶红军,邹兵,杜意平.2002.刺五加叶皂甙诱发肝癌细胞凋亡的研究[J].临床肝胆病杂志,18(3):162-163.
104.阴健,郭力弓.1993.刺五加-中药现代研究与临床应用[M].北京:学苑出版社,441-420.
105.余升红.2006.衰老与P16基因[J].中国优生与遗传杂志,14(9),3-4.
106.袁学千,王淑梅,高权国.2004.刺五加多糖增强鼠免疫功能的实验研究[J].中医药学报,32(4):48-49.
107.曾昭淳,马厚勋,曾繁荣.2000.不同年龄大鼠组织NO含量和NOS活性的变化与衰老之间的关系[J].中国老年学杂志,20(5):305-307.
108.战术,孙丰文,邵春杰,等.1996.刺五加叶皂苷单体SC3对培养大鼠心肌细胞自发性搏动及动作电位的影响[J].中国药学杂志,31(7):401-403.
109.张兵,侯家骥.1995.大鼠海马CA1区锥体神经元在衰老过程中的超微结构变化[J].神经解剖学杂志,11(3):249-251.
1l0.张东杰,冯昆,张爱武,等.2003.刺五加茶饮料抗疲劳作用的实验研究[J].营养学报,25(3):309.
111.张芳红,钟静芬,金家骅,等.1994.齐墩果酸在甘肃产八种五加科植物中的分布规律[J].中药材,17(9):29-31.
112.张敬一,杨惠敏,付琳杰,等.2001.刺五加多糖对小鼠Lewis肺癌的实验性干预作用研究[J].癌变畸变突变,13(4):270.
113.张莅霞,刘泓,董建平.1994.无梗红毛五加皮挥发油化学成分的研究[J].中国医学杂志,29(2):83-86.
114.张莅霞,刘淞.2001.红毛五加茎皮、叶及果实挥发油的GC-MS比较分析[J].中国中医基础科学杂志,7(5):24-27.
115.张曼颖,安继红,李昌辉.2002.刺五加叶皂甙诱导肺癌细胞凋亡的研究[J].吉林大学学报(医学版),28(1):37-39.
116.张松,王留兴,樊青霞,等.2007.刺五加叶皂苷联合冬凌草甲素对人食管癌Eca-109细胞的生长抑制作用[J].肿瘤基础与临床,20(3):226-229.
117.张熙,李文彬,张炳烈,等.1990.D-gal亚急性中毒大鼠拟衰老改变[J].中国药理学与毒理学杂志,4(4),309-310.
118.张玉华,韩丛成,曲绍春,等.2002.刺五加叶时大鼠实验性心肌梗死的保护作用[J].中国新药杂志,11(9):695-697.
119.赵俊霞,闰永鑫,赵娟,等.2008.刺五加多糖诱导人小细胞肺癌H446细胞凋亡[J].细胞生物学杂志,30(2):239-242.
120.赵余庆,柳江华.1989.刺五加中脂肪酸类和酯类成分的分离与鉴定[J].中医药学报,3:55-57.
121.郑春英,刘松梅,李宏涛,等.2007.胶束电动毛细管电泳同时检测刺五加中紫丁香苷及绿原酸的含量[J].中国药学杂忠,42(16):1248-1251.
122.郑丽杰,钱东华,戴洪龄.1994.红细胞膜的脂质过氧化物与衰老[J].白求恩医科大学学报,20(1):20-21.
123.郑日男,金海艳,裴风郁.1998.刺五加对胃缺血再灌注损伤防护作用的实验研究[J].中国中西医结合脾胃杂志,6(4):226-228.
124.郑荣梁.1992.衰老的自由基学说[J].实用老年医学,6(1):31-33.
125.周逸,唐其柱,史锡滕,等.2005.刺五加叶皂甙预处理对供心保存的实验研究[J].中国微循环,9(1):30-32.
126.邹承鲁主编.2000.当代生物学[M].北京:中国致公出版社,394-396.
127.Robert Goldman Ronald Klatz.2005.抗衰老革命[M].沈阳:辽宁科技出版社,10-11.
128.Adamas CS,Horron WE JR.1998.Chondrocyte Apoptosislncreases with Age in the Articular Catilage of AdultAnimals[J].Anat Rec,250(4):418-425.
129.Albina JE,Abate JA,Henry WL,et al.1991.Nitric oxide production is required for murine resident peritoneal macrophages to suppress mitogen-stimulated T cell proliferation.Role of IFN-gamma in the induction of the nitric oxide-synthesizing pathway[J].J Immunol,147(1):144-148.
130.Aleorta DA,XiongY.1996.Invovement of the cyclin-dependent kinaseinhibitorp 16~((INK4a)) in replicative seneseence of normal human fibroblasts[J].Proc Nad Sead Sci USA,93(24):13742-13747.
131.Allan LG,Arabinda G,Marion MZ,et al.1972.Purification and Biological Activity of Thymosin,a Hormone of the Thymus Gland[J].Proc Natl Acad Sci U S A,69(7):1800-1803.
132.Anna VM,Shalom GS,Nancy MJ,et al.2006.Increasing p16~(INK4a) expression decreases forebrain progenitors and neurogenesis during ageing[J].Nature,443(28),448-452.
133.Baker SJ,Reddy P.1996.Transducers of life and death:TNF receptor superfaraily and associated proteins[J].Oncogene,12( 1 ):21-29.
134.Beckman JS,Beckman TW,Chen J,et al.1990.Apparent Hydroxyl Radical Production by Peroxynitrite:Implications for Endothelial Injury from Nitric Oxide and Superoxide[J].Proc Natl Acad Sci USA,87(9):1620-1624.
135.Biesalski HK.2002.Free radical theory of aging[J].Curr Opin Clin Nutr Metab Care,5(1):5-10.
136.Bodey B.Bodey B.Siegel S E,et al.1999.MoIecular Biological Ontogenes is of the Thymic Ticulo-epithelial Cell Network during the Organization of the Cellular Microenvironment[J].In vivo (Athens,Greece) ,13(3):267-294.
137.Bodnar AG,Ouellette M,Frolkis M,et al.1998.Extension of life-span by introduction of telomerase into normal human cells[J].Science,279(5349):349-352.
138.Bruunsggaard H,Pederson AN,SchrollM,et al.1999.Impaired production of proinflammatory cytokines in resonse to lopopolysaccharides(LPS) stimu-lation in elderly humans[J].Clin Exp Immunol,118(2):235-241.
139.Cao SX.Dhahbi JM.Mote PL,et al.2001.Genomic profiling of short and long-term caloric restriction effects in the liver of aging mice[J].Proc Natl Acad Sci U S A,98( 19):10630-10635.
140.Cristofalo VJ.Volker C.Francis MK,et al.1998.Age-dependent modifications of gene expression in human fibroblasts[J].Crit Rev Eukaryot Gene Expr,8(1):43-80.
141.Das N,Levine RL,Orr WC,et al.2001 .Selectivity of protein oxidative damage aging in Drosophila melanogaster[J].Biochem J,360(1):209-216.
142.Dawson VL,Dawson TM.Bartley DA,et al.1993.Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures[J].J Neurosci Jun,13(6):2651 2651-2661.
143.Dimiri GP,Lee X,Basile G,et al.I995.A biomarker that identifies senescent human cells in culture and in aging skin in vivo[J].Proc Natl Acad Sci USA,92(20):9363-9367.
144.Dowdy SF.Hinds PW.Louie K,et a 1.1993.Physical interaction of the retinoblastoma protein with human D cyclins[J].Cell,73(7):499-511.
145.Egashira K,Inou T,HirookaY,et al.1993.Effects of age on endothelium_dependent vasodilation of resistance coronary artery by acetylukoline in humans[J].Cireulation,88(1):77-81.
146.Elisabeth B,Sylvie G,Denis M,et al.1999.Alterations of Rb Pathway (Rb-p16~(INK4)-Cyclin D1) in Preinvasive Bronchial Lesions[J].Clinical Cancer Research,5(2):243-250.
147.Fahn S,Cohen G.1992.The oxidative stress hypothesis in parkinsons disease:evedenee supporting it[J].Ann Neurol,32(6):804-812.
148.Ferrini M,Magee TR,Vernet D,et a 1.2001.Aging-related expression of inducible nitric oxide synthase and markers of tissue damage in the rat penis[J].Biol Reprod,64(3):974-982.
149.Franceschi C,Monti D.Sansoni P,et al.1995.The immunology of exceptional individuals:the lesson of centenarians[J].Immunol Today,16( 1):12-16.
150.Gentiloni SN.Mazzonc M,Portale C,et al.2001.Nitric oxide:ageneral review about the different roles of this innocent radial[J].Minerva Med,92(3):167-171.
151.Gerhard M,Roddy MA.Creager SJ,et al.1996.Aging progressively impair Sendothelium-dependent vasodilation in forearm resistance vessels of humans[J].Hypertension,27(4):849-853.
152.Giardino R,Giavaresi G,Fini M,et al.2002.The role of different chemical modifications of superoxide dismutase in preventing a prolonged muscular is chemislreperfusion injury[J].Artif Cells Blood Immubiol Biotechmol,30(3):189-198.
153.Ginaldi L,De Martinis M,D'Ostilio A,et al.1999.The immune system in the elderly Ⅲ Innate immunity[J].Immunol Res,20(2):117-126.
154.Ginaldi L.Loreto MF.Comi MP,et al.2001.Immunosenescence and infectious diseases[J].Microbes Infect,3(10):851-857.
155.Gorczynski RM.Cindar B,Ramakrishna V,et al.1997.An antibody specific for interleukin-6 reverse age associated changes in spontaneous and induced cytokine production in mice [J].Immunology,92(1):20-25.
156.Gunnar Skarping,Marianne Dalene.1995.Determination of 4,4-methylenediphenyldianiline(MDA) and identification of isomers in technical-grade MDA in hydrolysed plasma and urine from workers esposed to methylene diphenyl diisocyanate by gas chromatograp-hy-mass soectrometry[J].Journal of Chromatography B,663(2):209-216.
157.Hannun YA.Luberto C.2000.Ceramide in the eukaryotic stress response[J].Trends Cell Biol.10 (2):73-80.
158.Harman D.1981.The aging process[J].Proc Natl Acad Sci USA,78(11):7124-7128.
159.Hashimoto S,Oehs RL.1998.Chondrocyte-derived ApoptoticBodies and Calcification of Articular Cartilage[J].Proc Natl Acad Sci USA,95(6):3094-3095.
160.Hinds PW.Mittnacht S,Dulic V,et al.1992.Regulation of retinoblastoma protein functions by ectopic expression of human cyclins[J].Cell,70(6):993-1006.
161.Ian'kova Vl,Ivanova IL.2003 .Age-related changes of lipids pectrum.level of lipid peroxidation,and antioxidant defence in the liver and blood of rats[J].Ross Fiziol Zh Im I M Seehenova,89(7):828-836.
162.Johan Bjorksten,William J.Champion.1942.Mechanical Influence upon Tanning[J].Am.Chem.Soc,64 (4),868-869.
163.John DM .Jianguo W,Tong Z,et al.1997.Cell death and longevity amplications of Fas - mediated apoptosis in T cell senescence [J].Immunol Rev,160 (1):19-25.
164.Jorge D.Erusalimsky DJ.Kurz.2005.Cellular senescence in vivorlts relevance in ageing and cardiovascular disease[J].Exp Gerontol,40(2):634-642.
165.Krishnamurthy J,Ramsey MR,Ligon KL,et al.2006.p16~(INK4a) induces an age-dependent decline in islet regenerative potential[J].Nature,443(7110):453-457.
166.Krishnaraj R.1997.Senescence and cytokines modulate the NK cell expression[J].Mech Aging Dev,96(1-3):89-101.
167.Kuo J,HC Yang,IS Cheng,et al.2005.Supplementation of eleutherococcus senticosus (CIWUJIA) on anti-fatigue function in human.The 18th International Congress of Nutrition in South Africa[C],11,19-23.
168.L.Hayflick,Moorehead PS.1961.The serial cultivation of human diploid cell strains[J].Exp Cell Res,25(12),585-621.
169.Lee CK,Klopp RQWeindruch R,et al.1999.Gene expression profile of aging and its retardation by caloric restriction[J].Gelence,285(5432):1390-1393.
170.Lin HZ,Yang SQ.Chukaree C,et al.2000.Meformin fatty liver disease in obese,leptin deficient mice[J].Nat Med,6(9),998-1003.
171.Luo Y,Umegaki H.Dopamine Induces Apoptosis.1998.Through an Oxidation Involved SAPK / JNK Activation Pathway[J].J Biol Chem,273(6):3756-3764.
172.Manolagas S C.Cellular and Molecular.1998.Mechanisms of Osteporosis[J].Aging,10(3):182-190.
173.Martin SJ,Green DR,Cotter TG1994.Dicing with death:dissecting the components of the apoptosis machinery[J].Trends Biochem Sci Jan,19(1):26-30.
174.Masoro EJ.1998.Hormesis and the antiaging action of dietary restriction[J].Exp Gerontol,33 (1-2):61-66.
175.Morreau H,Galjart NJ,Gillemans N,et al.1989.Alternative spli_cing of beta_galactosidase mRNA generates the classic lysosomal enzyme and a beta_galactosidase_related protein[J].J Biol Chem,264(34):20655-20663.
176.Norrback KF,Enblad G,Erlanson M,et al.1998.Telomerase activity in Hodgkin a disease[J].Blood,92 (2):567-574.
177.Orgel LE.1963.The maintenance of the accuracy of protein synthesis and its relevance to aging[J].Proc Nat Acad Sci USA,49(4):517-521.
178.Park SY.Chang SY.Yook CS.et al.2000.New3,4-seco-lu-pane-type triterpene glycosides from Acanthopanax senticosus forma inermis[J].J Nat Prod,63(12):1630-1633.
179.Parker RJ,Berkowitz BA,Lee CH,et al.1978.Vascular relaxation,aging and thyroid hormones[J].Mech Ageing Dev,8(6):397-405.
180.Pendergrass WR ,Lane MA ,Bodkin NL,et al.1999.Cellular proliferation potential during aging and caloric restration in rhesus monkeys[J].J cell Phsiol,180(2):123-130.
181.Pinkston-Gosse J.Kenyon C.2007.DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans Nature Genetics[J].Nat Genet,39(11):1403-1409.
182.Pratieo D.2002.Lipid peroxidation and the aging process[J].Sei Aging Knowledge Environ,2002(50):5-9.
183.Prolla TA.2002.DNA microarray analysis of the aging brain[J].Chem Senses,27(3):299-306.
184.Rider DA.Sinclair AJ,Young SP,et a 1.2003.Oxidative inactivation of CD45 protein tyrosine phosphatase may contribute to T lymphocyte dysfunction in the elderly [J].Mech Ageing Dev,124:191-198.
185.Rusting,R.L.1992.Trends in biology.Why do we age[J]?Sci Am,267(6):130-141.
186.Sandhu C,Donovan J.Bhattacharya N,et al.2000.Reduction of Cdc25A contributes to cyclin El-Cdk2 inhibition at senescence in human mammary epithelial cells[J].Oncogene,19(47):5314-5323.
187.Sandhu SK,Kaur G2002.Alterations in oxidative stress scavenger system in aging rat brain and lumphocytes[J].Biogerontology,3(3):161 -173.
188.Sarkar G,Bolander ME.1995.Telomeres,telomerase,and cancer[J].Science,268 (5214):1115-1117.
189.Segre D,Miller RA,Abraham GN.et al.1989.Aging and the Immune system.J Gerontol,44(6):164-168.
190.Shan BE.Yoshita Y.Sugiura T ,et al.1999.Suppressive effect of Chinese medicinal herb,Acanthopanax gracilistylus,extract oil human lymphocytes in vitro[J].Clinical & Experimental Immunology,118(1):41-48.
191.Shao CJ.Ryoji K,Xu J D,et al.1989.Saponins from Leaves of Acanthopanax Senticosus Harms,CiwujiaII.Structures of Ciwujia nosides B,Al,A2,A3,A4andD3[J].Chem Pharm Bull,37(1):42-46.
192.Shelton DN ,Chang E.Whittier PS,et al.1999.Microarray analysis of replicative senescence.[J]Current biology,9( 17):939-945
193.Shi X,Dai C,Nuttall AL.2003.Altered expression of inducible nitric oxide synthase(iNOS)in the cochlea[J].Hear Res,177( 1 -2):43-52.
194.Siles E.Martinez-Lara E,CafihueIo A,et al.2002.Age-related changes of the nitric oxide system in the rat brain[J].Brain Res,956(2):385-392.
195.Sohal RS,Ku HH,Agarwal S,et al.1994.0xidative damage,mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse[J].Mech.Ageing Dev,74(1-2):121-133.
196.Song X,Bao M,Li D,and YM Li.1999.Advanced glycation in D-galactose induced mouse aging model[J].Mech Ageing Dev,108(3):239-251.
197.Stein GH,Beeson M.Gordon L.1990.Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts[J].Science,249(4969):666-669.
198.Stephen Bachows Ki.Yong Xu,Donald ES,et al.1998.Role of Oxidative Stress in the Selective Toxicity of Dieldrin in the Mouse Liver[J].Toxicology and Applied Pharmacology,150(2):301-309.
199.Tahira F and Akhlaq A.2008.Aging:an important factor for the pathogenesis of neurodegenerative diseases[J].Mechanisms of Ageing and Development,130(4):203-215.
200.Titia de Lange.1998.Telomeres and senescence:ending the debate[J].Science,279(3):334-335.
201.van Dam MJ,de Groot E,clee sM,et al .2002.Association between increased arterial-wall thickness and impairment in ABCAl-driven cholesterol efflux:an observational study[J].Lancet,359(9300):37-4 2.
202.Venable ME,Lee JY,Smyth MJ,et al.1995.Role of ceramide in cellular senescenee[J].J Biol Chem,270(51 ):30701-30708.
203.Wang E,Lacelle C,Xu S,et al.2002.Designer microarrays:from soup to nuts[J].J Gerontol A Biol Sci Med Sci,57(11):B400-B405.
204.Warner HR,Hodes R,Pocinki K.1997.What does cell death have to do with aging [J]?J Am Geriatr Soc,45(9):1140-1146.
205.Weindruch R,Kayo T,Lee CK,et al.2001.Microarray profiling of gene expression in aging and its alteration by caloric restriction in mice[J].J Nutr,131(3):918S-923S.
206.Weksler ME.2000.Changes in the B-cell repertoire with age[J].Vaccine,18(16):1624-1628.
207.Weng NP.2006.Ageing of the immune system:how much can the adaptive immune system adapt[J].Immunity,24(5):495.
208.Yang FF.Yuan SG,Yew DT.2008.Use of functional magnetic resonance imaging (blood oxygenation level-dependent imaging,diffusion tensor imaging and magnetic resonance spectroscopy) in brain development research.Neuroembryol aging,5(8):56-59
209.Zaciragic A,Nakasicindic E,Hadzovic A,et al.2004 .Average values of electrocardiograph parameters in healthy,adult Wistar rats[J].Med Arh,58(5):268-270.
210.Zissel G,Schlaak M,Muler-Quemheim J.1999.Age.related decrease in accessory cell function of hunmn alveolar macrophages[J].J Invest Med,47(1 ):51-56.