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蓝莓花色苷对CP致脏器损伤的保护及抗衰老作用研究
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摘要
蓝莓是杜鹃花科(Ericaceae)越橘属植物,在我国有丰富的资源。研究表明,蓝莓果实的主要活性成分为花色苷类物质,长期食用可以消除用眼疲劳,保护视力,并且具有抗炎、抗氧化、抗溃疡、抗衰老和抗癌等生理活性。本文对蓝莓花色苷进行了较系统的研究,在课题组研究的基础上,研究了蓝莓花色苷的提取工艺,通过溶剂法和酶法研究蓝莓花色苷的提取工艺;并研究了蓝莓花色苷在环磷酰胺所致大鼠心脏、肺与肝脏损伤模型的保护作用及抗衰老模型中的保健功效,为更好地开发和利用蓝莓资源提供理论支持。主要研究结论如下:
     1.采用酸性乙醇对蓝莓中花色苷进行提取,在单因素的基础上通过响应面试验方法确定蓝莓花色苷提取所需最佳提取条件为:提取液乙醇体积分数60.65%,料液比1g:20.65ml,提取时间122.53mm, pH3.0,提取温度50℃,提取两次。在此条件下进行提取,确定蓝莓冻果花色苷含量约为327.35mg/100g。
     2.通过环磷酰胺(CP)对大鼠进行造模,研究了蓝莓花色苷对CP所致心脏损伤的保护作用。本试验从血清心肌酶谱、组织病理学二个方面研究了蓝莓花色苷对CP所致心脏损伤作用的保护作用,通过对抗氧化酶SOD活性、MDA水平及凋亡蛋白的测定,探讨了保护机制。
     3.研究了蓝莓花色苷对环磷酰胺所致肺损伤的保护作用。探讨了蓝莓花色苷对CP所致的肺损伤的拮抗作用,实验结果显示:蓝莓花色苷改善了CP所致的肺损伤的病理变化,减轻了炎性渗出,减少了促炎因子的表达,增加了抑炎因子的活性,同时减轻了过氧化损伤,表明蓝莓花色苷对CP所致的肺损伤有一定的保护作用。
     4.研究了蓝莓花色苷对环磷酰胺所致肝损伤的保护作用。本试验从血清指标、组织病理学两个方面研究了蓝莓花色苷对CP所致肝脏损伤作用的保护作用。病理结果表明,CP导致大鼠肝脏中央静脉周围可见肝细胞出现弥漫性空泡变性,血清测试结果发现,CP导致大鼠ALT、AST与ALP值均显著升高,这与其它人的报导一致。与模型组相比较,蓝莓花色苷组病理变化、血清酶学指标都有所改善,证明了蓝莓花色苷对CP导致的肝脏损伤具有明显的保护作用。
     5.研究了低、高剂量组的蓝莓花色苷对小鼠学习能力的影响,发现两个剂量组均能够显著的改善实验中衰老小鼠的学习记忆障碍,提高小鼠的空间分辨能力,并能够延长衰老小鼠的游泳时间;延长小鼠跳台实验中小鼠的潜伏期,并减少错误次数;提高Y迷宫实验中大鼠的学习能力;并可缩短明暗箱实验中大鼠的潜伏期。这些结果表明低、高剂量的蓝莓花色苷能够有效的改善衰老小鼠和大鼠的学习记忆障碍,提高学习记忆能力。
Blueberry belongs to Ericaceae Vaccinium.spp and is abundant over our country. It has been studied that there are abundant anthocyanins in blueberries and many physiological and officinal functions in blueberries such as eliminating eye fatigue, protecting the eyesight, antioxidant, anti-aging, anti-ulcer, anti-inflammatory and anti-cancer et al. In this paper, blueberry anthocyanins have been analyzed by pH differential method; the extraction technology of blueberry anthocyanins is optimized by response surface method with acidic alcohol as extractant.
     The main conclusions are as follows:
     1. The blueberry pigments is extracted by acidic alcohol. On the basis of single factor test, the optimization of various factors and their interaction effect is analyzed by response surface method. The best extraction parameters are:ethanol content is60.65%, material-solvent ratio is1g:20.65ml, extraction time is122.53min, the value of PH is3.0extraction temperature is50℃, extraction twice. Under this extraction condition, the determination of the blueberry anthocyanins is327.35mg/100g.
     2. The heart protective effects of the blueberry anthocyanins (20mg/kg and80mg/kg, ig) are investigated in CP-induced heart injury model (100mg/kg, ip). The protective role of the blueberry anthocyanins is demonstrated by the tests from two aspects—serum myocardial enzyme spectrum and histopathologic study. The blueberry anthocyanins show protective effect on heart damage. The mechanism is investigated by the change of SOD activity of antioxidant enzymes and MDA level, and the apoptosis protein of Bax and Bcl-2with westernblot, the results showed blueberry anthocyanins increased the SOD activities and lower MDA level, and decreased the proapoptosis protein Bax expression and increased the antiapotosis protein Bcl-2expression, the results indicate that antioxidative stress and antiapoptosis are involved in the protective function of blueberry anthocyanins.
     3. Blueberry anthocyanins have been studied on the lung injury caused by cyclophosphamide. The rats are the same with described in heart protective test. The experimental results show that:blueberry anthocyanins improve the pathological changes of lung injury caused by CP, reduce inflammatory exudation and the expression of proinflammatory factors, increase the activity of the suppresve inflammatory factors, and reduce the peroxidation damage at the same time, indicating that anthocyanins of blueberry possess certain protective effect in lung injury caused by CP.
     4. Blueberry anthocyanins have been studied in liver injury caused by cyclophosphamide. The protective effects of the test are from two aspects called serum index and histopathological study. The results show that the CP treated rat liver with visible diffuse vacuoles degeneration of hepatic cells around the central vein, serum test results show that ATL AST and ALP values are significantly increased in CP treated rats, which are consistent with other researchers' results. Pathological changes of serum enzymology indexes are improved in blueberry anthocyanins groups, which demonstrat the blueberry anthocyanins have the outstanding clear protective role in liver injury.
     5. The influence of high and low dose group of blueberry anthocyanins on learning ability has been investigated in mice, the results show that two groups can significantly improve the performances of aging mice in Morris water maze experiment, and extends the diving platform incubation period, besides, it can decrease the data error, and improve the learning ability of rat in Y maze experiment and also; can shorten latent period of rats in the light-dark transition test. Blueberry anthocyanins can increase the aging mice swimming time. The results indicate that the blueberry anthocyanins can effectively improve the aging mice and rats learning and memory impairment, and increase the muscle function.
引文
1. Almeida, J. R., E. D'Amico, A. Preuss, F. Carbone, C. De Vos, B. Deiml, F. Mourgues, G. Perrotta, T. C. Fischer & A.G. Bovy (2007) Characterization of major enzymes and genes involved in flavonoid and proanthocyanidin biosynthesis during fruit development in strawberry (< i> Fragariax< i> ananassa). Archives of biochemistry and biophysics,465,61-71.
    2. Bakowska, A., A. Z. Kucharska & J. Oszmianski (2003) The effects of heating, UV irradiation, and storage on stability of the anthocyanin-polyphenol copigment complex. Food Chemistry,81,349-355.
    3. Basu, A., M. Du, M. J. Leyva, K. Sanchez, N. M. Betts, M. Wu, C. E. Aston & T. J. Lyons (2010) Blueberries decrease cardiovascular risk factors in obese men and women with metabolic syndrome. The Journal of nutrition,140,1582-1587.
    4. Bridle, P. & C. Timberlake (1997) Anthocyanins as natural food colours—selected aspects. Food Chemistry,58,103-109.
    5. Chatterjee, A., T. Yasmin, D. Bagchi & S. J. Stohs (2004) Inhibition of Helicobacter pylori in vitro by various berry extracts, with enhanced susceptibility to clarithromycin. Molecular and cellular biochemistry,265,19-26.
    6. Cos, P., T. Bruyne, N. Hermans, S. Apers, B. DVanden & A. Vlietinck (2004) Proanthocyanidins in health care:current and new trends. Current medicinal chemistry,11,1345-1359.
    7. Cruickshanks, K. J., R. Klein & B. E. Klein (1993) Sunlight and age-related macular degeneration:the Beaver Dam Eye Study. Archives of Ophthalmology,111,514.
    8. de Pascual-Teresa, S., D. A. Moreno & C. Garcia-Viguera (2010) Flavanols and anthocyanins in cardiovascular health:a review of current evidence. International journal of molecular sciences,11, 1679-1703.
    9. Feng, R., H.-M. Ni, S. Y. Wang, I. L. Tourkova, M. R. Shurin, H. Harada & X.-M. Yin (2007) Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress. Journal of Biological Chemistry,282,13468-13476.
    10. Kong, J.-M., L.-S. Chia, N.-K. Goh, T.-F. Chia & R. Brouillard (2003) Analysis and biological activities of anthocyanins. Phytochemistry,64,923-933.
    11. Mainster, M., W. Ham Jr & F. Delori (1983) Potential retinal hazards. Instrument and environmental light sources. Ophthalmology,90,927-932.
    12. Matsumoto, H., H. Inaba, M. Kishi, S. Tominaga, M. Hirayama & T. Tsuda (2001) Orally administered delphinidin 3-rutinoside and cyanidin 3-rutinoside are directly absorbed in rats and humans and appear in the blood as the intact forms. Journal of agricultural and food chemistry,49,1546-1551.
    13. Osman, N., D. Adawi, S. Ahrne, B. Jeppsson & G. Molin (2007) Endotoxin-and d-galactosamine-induced liver injury improved by the administration of< i> Lactobacillus,< i> Bifidobacterium and blueberry. Digestive and liver disease,39,849-856.
    14. Rein, M. (2005) Copigmentation reactions and color stability of berry anthocyanins. University of Helsinki.
    15. Renaud, S. d. & M. de Lorgeril (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. The Lancet,339,1523-1526.
    16. Riso, P., D. Klimis-Zacas, C. Del Bo, D. Martini, J. Campolo, S. Vendrame, P. M(?)ller, S. Loft, R. De Maria & M. Porrini (2012) Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors. European journal of nutrition,1-13.
    17. Sakaida, H., K. Nagao, K. Higa, B. Shirouchi, N. Inoue, F. Hidaka, T. Kai & T. Yanagita (2007) Effect of Vaccinium ashei reade leaves on angiotensin converting enzyme activity in vitro and on systolic blood pressure of spontaneously hypertensive rats in vivo. Bioscience, biotechnology, and biochemistry,0708030528.
    18. Seeram, N. P., L. S. Adams, Y. Zhang, R. Lee, D. Sand, H. S. Scheuller & D. Heber (2006) Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro. Journal of agricultural and food chemistry,54, 9329-9339.
    19. Seeram, N. P., R. Schutzki, A. Chandra & M. G Nair (2002) Characterization, quantification, and bioactivities of anthocyanins in Cornus species. Journal of agricultural and food chemistry,50, 2519-2523.
    20. Suh, N., S. Paul, X. Hao, B. Simi, H. Xiao, A. M. Rimando & B. S. Reddy (2007) Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats. Clinical cancer research,13,350-355.
    21. Takami, Y, H. Uto, M. Takeshita, H. Kai, E. Akamatsu, A. Moriuchi, S. Hasegawa, M. Oketani, A. Ido & H. Kataoka (2010) Proanthocyanidin derived from the leaves of Vaccinium virgatum suppresses platelet-derived growth factor-induced proliferation of the human hepatic stellate cell line LI90. Hepatology Research,40,337-345.
    22. Wilms, L. C., A. W. Boots, V. C. de Boer, L. M. Maas, D. M. Pachen, R. W. Gottschalk, H. B. Ketelslegers, R. W. Godschalk, G. R. Haenen & F. J. van Schooten (2007) Impact of multiple genetic polymorphisms on effects of a 4-week blueberry juice intervention on ex vivo induced lymphocytic DNA damage in human volunteers. Carcinogenesis,28,1800-1806.
    23.方允中&郑荣梁(2002)自由基生物学的理论与应用.科学出版社.
    24.王豫萍,程明亮,吴亚云,张宝芳&吴君(2010)蓝莓对大鼠肝星状细胞增殖,活化的影响及机制探讨.中华医学杂志,90,2504-2508.
    25.王豫萍,程明亮,张宝方&吴君(2013)蓝莓对肝纤维化大鼠PPARy和PDGF—B表达的影响.中华医学杂志,93,218-221.
    26.王豫萍,张宝方,周明玉,易平,吴君&程明亮(2009)蓝莓预防大鼠肝损伤实验研究.肝脏,14,33-35.
    27.王姗姗,孙爱东&李淑燕(2010)蓝莓的保健功能及其开发应用[J].中国食物与营养,6,17-20.
    28.宋毅,宫媛媛,李彩红&吴星伟(2008)灵杞黄斑颗粒对光损伤大鼠视网膜氨基酸类神经递质水平的影响.上海中医药杂志,42,62-65.
    29.李亚东,姜惠铁,张志东&吴林(2001)中国蓝莓产业化发展的前景.沈阳农业大学学报(社会科学版),3,39-42.
    30.李亚东&张志东(2002)蓝莓果实的成分及保健机能.中国食物与营养,27-28.
    31.李颖畅&孟宪军(2007)蓝莓花色苷抗氧化活性的研究.食品与发酵工业,33,61-64.
    32.李颖畅,孟宪军,孙靖靖&于娜(2008)蓝莓花色苷的降血脂和抗氧化作用[J].食品与发酵工业,34,44-48.
    33.李颖畅,宣景宏&孟宪军(2007)蓝莓果中花色素苷的研究进展.食品研究与开发,28,178-180.
    34.李颖畅,齐凤元&冯彦博(2009)金属离子对蓝莓花色苷的影响.食品与机械,25,52-55.
    35.孟宪军,于欣灵,孙仁艳&张锐(2011)蓝莓提取物对小鼠记忆力及抗衰老作用的研究.沈阳农业大学学报,42,740-742.
    36.孟宪军,毕菀芩,张琦&李斌(2013)蓝莓花色苷对大鼠视网膜光损伤的保护作用及其机制.食品科学,34,243.
    37.帕提古丽,马合木提&高莉,史博(2004)酸浆花萼色素的提取及理化性质研究[J].食品科学, 25,35-35.
    38.姚伙旺,曾秋平,劳永民,刘顺枝&胡位荣(2006)食品添加剂对荔枝果皮花色素苷稳定性影响的研究.食品科学,27,152-156.
    39.胡雅馨,李京&惠伯棣(2001)蓝莓果实中主要营养及花青素成分的研究.机械,4,5-8.
    40.唐阳(2005)蓝莓小档案.饮食科学,29-29.
    41.莫小曼(2000)蓝莓营养解析.中国食品,24,17-17.
    42.刘红锦,刘小莉&周剑忠(2009)蓝莓中花色苷提取及其抗氧化活性研究[J].江苏农业学报,25,1347-1350.
    43.叶小利,李坤培&李学刚(2002)酸碱度对紫色甘薯花色素稳定性影响的研究.食品工业科技,23,38-39.
    44.张燕,谢玫珍&廖小军(2005)热和紫外辐照对红莓花色苷稳定性的影响.食品与发酵工业,31,37-40.
    45.张宝芳,程明亮,王豫萍&穆茂(2010)蓝莓对大鼠肝纤维化TGF-β1/Smads信号通路的影响.传染病信息,148-153.
    46.聂芊&吴春(2002)辅色素对笃柿天然色素稳定性的影响.食品研究与开发,23,31-32.
    47.贺强&吴立仁(2010)蓝莓果实中营养成分的生物学功能.北方园艺,24,222-224.
    48.郑光耀(2000)葡萄籽原花青素提取物的生理活性,药理作用及其应用.林产化工通讯,34,28-33.
    49.陆爽,程明亮,李宏&吴君(2012)蓝莓对免疫性肝纤维化大鼠细胞色素P4502E1表达的影响.中华肝脏病杂志,20,497-502.
    50.陈介甫,李亚东&徐哲(2010)蓝莓的主要化学成分及生物活性[J].药学学报,45,422-429.
    51.陈健,孙爱东,高雪娟,陶晓赞&王姗姗(2011)蓝莓花青素的提取及抗氧化性的研究[J].北京林业大学学报,33,126-129.
    52.马萍,纪中,纪长伟,戚汉平,黄伟&曹永刚(2013)蓝莓花色苷预处理对大鼠心肌梗死的保护作用.中国比较医学杂志,23,49-52.
    53. Mazza, G. & R. Brouillard (1987) Color stability and structural transformations of cyanidin 3, 5-diglucoside and four 3-deoxyanthocyanins in aqueous solutions. Journal of agricultural and food chemistry,35,422-426.
    54. Mazza, G., J. E. Cacace & C. D. Kay (2004) Methods of analysis for anthocyanins in plants and biological fluids. Journal of AOAC international,87,129-145.
    55. Pinelo, M., M. Rubilar, M. Jerez, J. Sineiro & M. J. Nunez (2005) Effect of solvent, temperature, and solvent-to-solid ratio on the total phenolic content and antiradical activity of extracts from different components of grape pomace. Journal of Agricultural and Food Chemistry,53,2111-2117.
    56.王晖&刘佳佳(2003)银杏黄酮的酶法提取工艺研究.中药材,26,887-888.
    57.李金星&胡志和(2013)蓝莓花青素的研究进展.核农学报,6,0817-0822.
    58.李颖畅,孟宪军,修英涛,宣景宏&冯颖(2007)蓝莓果中花色昔的提取工艺研究[J].食品科技,11,73-76.
    59.胡雅馨,李京&惠伯棣(2001)蓝莓果实中主要营养及花青素成分的研究.机械,4,5-8.
    60.唐传核.2005.植物生物活性物质.化学工业出版社.
    61.郝建军,刘延吉&陈贵(2001)植物生理学试验技术.沈阳:辽宁科学技术出版社.
    62.高梓淳,吴涛,陈卫&郑晓冬(2013)蓝莓花色苷提取与纯化工艺的研究.食品与发酵科技,49,1-5.
    63.蔡俊(2005)酶在番茄红素提取过程中的应用研究.湖北工业大学学报,20,8-10.
    64.霍琳琳,苏平&吕英华(2005)分光光度法测定桑葚总花色苷含量的研究[J].酿酒,32,88-89.
    65.薛伟明&张效林(1999)膜纯化—分光光度法测定侧柏叶总黄酮含量.西北大学学报:自然科学版,29,37-40.
    66.刘洪海,张晓丽,杜平&张希波(2009)pH示差法测定烟73葡萄中花青素含量[J].中国调味品,34,110-111.
    67.孙艳华&苗靖(2006)酶法提取荞麦茎叶中黄酮的研究.食品工业,27,16-18.
    68.张立娟&于国萍(2005)细胞破壁酶在黑木耳多糖提取中作用条件的研究.食用菌,3.
    69.张华&李景琳(1998)越桔红色素提取工艺的研究.辽宁农业科学,8-12.
    70.闫巧娟,韩鲁佳&江正强(2005)纤维素酶法提取黄芪多糖[J].中草药,36,1804-1807.
    71. Asiri, Y. A. (2010) Probucol attenuates cyclophosphamide-induced oxidative apoptosis, p53 and Bax signal expression in rat cardiac tissues. Oxidative medicine and cellular longevity,3,308-316.
    72. Basu, A., M. Du, M. J. Leyva, K. Sanchez, N. M. Betts, M. Wu, C. E. Aston & T. J. Lyons (2010) Blueberries decrease cardiovascular risk factors in obese men and women with metabolic syndrome. The Journal of nutrition,140,1582-1587.
    73. Chargari, C., K. M. Kirov, M. A. Bollet, N. Magne, L. Vedrine, S. Cremades, P. Beuzeboc, A. Fourquet & Y. M. Kirova (2011) Cardiac toxicity in breast cancer patients:From a fractional point of view to a global assessment. Cancer treatment reviews,37,321-330.
    74. Chen, Y., S. Zhang, G Peng, J. Yu, T. Liu, R. Meng, Z. Li, Y. Zhao & G. Wu (2013) Endothelial NO synthase and reactive oxygen species mediated effect of simvastatin on vessel structure and function: Pleiotropic and dose-dependent effect on tumor vascular stabilization. International journal of oncology,42,1325.
    75. Coffin, A. B., E. W. Rubel & D. W. Raible (2013) Bax, Bcl2, and p53 differentially regulate neomycin-and gentamicin-induced hair cell death in the zebrafish lateral line. Journal of the Association for Research in Otolaryngology,14,645-659.
    76. Croker, B. A., J. A. O'Donnell, C. J. Nowell, D. Metcalf, G Dewson, K. J. Campbell, K. L. Rogers, Y. Hu, G K. Smyth & J.-G. Zhang (2011) Fas-mediated neutrophil apoptosis is accelerated by Bid, Bak, and Bax and inhibited by Bc1-2 and Mcl-1. Proceedings of the National Academy of Sciences,108, 13135-13140.
    77. Hill, D. L (1975) A review of cyclophosphamide. Thomas Springfield, ILL, USA.
    78. Jnaneshwari, S., M. Hemshekhar, M. S. Santhosh, K. Sunitha, R. Thushara, C. Thirunavukkarasu, K. Kemparaju & K. S. Girish (2013) Crocin, a dietary colorant mitigates cyclophosphamide-induced organ toxicity by modulating antioxidant status and inflammatory cytokines. Journal of Pharmacy and Pharmacology.
    79. Mills, B. A. & R. W. Roberts (1979) Cyclophosphamide-induced cardiomyopathy. A report of two cases and review of the english literature. Cancer,43,2223-2226.
    80. Motawi, T. M., N. A. Sadik & A. Refaat (2010) Cytoprotective effects of DL-alpha-lipoic acid or squalene on cyclophosphamide-induced oxidative injury:An experimental study on rat myocardium, testicles and urinary bladder. Food and Chemical Toxicology,48,2326-2336.
    81. Nasiraei-Moghadam, S., B. Kazeminezhad, L. Dargahi & A. Ahmadiani (2010) Maternal oral consumption of morphine increases Bax/Bcl-2 ratio and caspase 3 activity during early neural system development in rat embryos. Journal of molecular neuroscience,41,156-164.
    82. Oboh, G. & O. O. Ogunruku (2010) Cyclophosphamide-induced oxidative stress in brain:Protective effect of hot short pepper (< i> Capsicum frutescens L. var.< i> abbreviatum). Experimental and Toxicologic Pathology,62,227-233.
    83. Pinder, M. C., Z. Duan, J. S. Goodwin, G. N. Hortobagyi & S. H. Giordano (2007) Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. Journal of Clinical Oncology,25,3808-3815.
    84. Riso, P., D. Klimis-Zacas, C. Del Bo, D. Martini, J. Campolo, S. Vendrame, P. M(?)ller, S. Loft, R. De Maria & M. Porrini (2012) Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors. European journal of nutrition,1-13.
    85. Shaik, A. H., S. Rasool, A. Vikram Kumar Reddy, M. Abdul Kareem, G. Saayi Krushna & K. Lakshmi Devi (2012) Cardioprotective effect of HPLC standardized ethanolic extract of< i> Terminalia pallida fruits against isoproterenol-induced myocardial infarction in albino rats. Journal of Ethnopharmacology,141,33-40.
    86. Shanmugarajan, T., M. Arunsundar, I. Somasundaram, E. Krishnakumar, D. Sivaraman & V. Ravichandiran (2008) Cardioprotective effect of Ficus hispida Linn, on cyclophosphamide provoked oxidative myocardial injury in a rat model. International Journal of Pharmacology,4,78-87.
    87. Turk, G., A. O. Ceribasi, F. Sakin, M. S(?)mez & A. Atessahin (2010) Antiperoxidative and anti-apoptotic effects of lycopene and ellagic acid on cyclophosphamide-induced testicular lipid peroxidation and apoptosis. Reproduction, Fertility and Development,22,587-596.
    88. Wang, X., X. Wang, L. Xiong, Y. Zhu, H. Chen, J. Chen, X. Wang, R. Li, Z. Guo & P. Li (2013) Salidroside improves Doxorubicin-Induced cardiac dysfunction by Suppression of Excessive Oxidative Stress and Cardiomyocyte Apoptosis:Doxorubicin Cardiotoxicity inhibited by Salidroside. Journal of cardiovascular pharmacology.
    89. Wu, C., R. Chen, X. S. Wang, B. Shen, W. Yue & Q. Wu (2013) Antioxidant and Anti-Fatigue Activities of Phenolic Extract from the Seed Coat of Euryale ferox Salisb. and Identification of Three Phenolic Compounds by LC-ESI-MS/MS. Molecules,18,11003-11021.
    90.余静,索有瑞,张生平,王琼英,常鹏&汪汉卿(2007)甘肃黄芪对多柔比星心肌病大鼠心肌组织部分基因表达的影响[J].中国药学杂志,42,437-440.
    91.李颖畅(2008)蓝莓花色苷提取纯化及生理功能研究[D].沈阳农业大学.
    92.李颖畅,孟宪军,孙靖靖&于娜(2008)蓝莓花色苷的降血脂和抗氧化作用[J].食品与发酵工业,34,44-48.
    93.易善永,南克俊,陈圣杰,卢创新&孔莺(2008)银杏叶提取物对多柔比星所致乳腺癌患者心脏毒性的干预作用.中国中西医结合杂志,28,68-69.
    94.刘华忠,王光,吴金龙,师莉莎,钟杰平&潘江球(2012)乌贼墨多糖对环磷酰胺致小鼠部分脏器损伤的缓解效应.中国现代应用药学,29,89-89.
    95.赵明宏,郭涛,宋洪涛,张晓虹&刘玉兰(2002)川芎嗪对小鼠环磷酰胺损伤的保护作用[J].中国医院药学杂志,22,717-718.
    96. Akbas, H.S., Timur, M., Ozben, T.(2006) Concurrent use of antioxidants in cancer therapy:an update. Expert Review of Clinical Immunology 2,931-939.
    97. Ashry, N.A., Gameil, N.M., Suddek, G.M. (2013) Modulation of cyclophosphamide-induced early lung injury by allicin. Pharmaceutical biology 51,806-811.
    98. Bornsek, S.M., Ziberna, L., Polak, T., Vanzo, A., Ulrih, N.P., Abram, V., Tramer, F., Passamonti, S. (2012) Bilberry and blueberry anthocyanins act as powerful intracellular antioxidants in mammalian cells. Food chemistry 134,1878-1884.
    99. Chakraborty, P., Sk, U.H., Murmu, N., Das, J.K., Pal, S., Bhattacharya, S. (2009) Modulation of cyclophosphamide-induced cellular toxicity by diphenylmethyl selenocyanate in vivo, an enzymatic study. J Cancer Mol 4,183-189.
    100. Chen, J., Sun, H., Sun, A., hua Lin, Q., Wang, Y., Tao, X. (2012) Studies of the protective effect and antioxidant mechanism of blueberry anthocyanins in a CC14-induced liver injury model in mice. Food and Agricultural Immunology 23,352-362.
    101. Chirumbolo, S. (2012) Plant phytochemicals as new potential drugs for immune disorders and cancer therapy:really a promising path? J Sci Food Agric 92,1573-1577.
    102. Crohns, M., Liippo, K., Kankaanranta, H., Moilanen, E., Alho, H., Kellokumpu-Lehtinen, P. (2009) 156P ANTIOXIDANTS AND MARKERS OF OXIDATIVE AND NITROSATIVE STRESS DURING COMBINATION CHEMOTHERAPY FOR SMALL CELL LUNG CANCER. Lung Cancer 64, S65.
    103. Cummings, K.W., Bhalla, S. (2013) Chemotherapy-Related Lung Injury, Lung Cancer Imaging. Springer, pp.181-188.
    104. Huang, C.-C., Aronstam, R.S., Chen, D.-R., Huang, Y.-W. (2010) Oxidative stress, calcium homeostasis, and altered gene expression in human lung epithelial cells exposed to ZnO nanoparticles. Toxicology in Vitro 24,45-55.
    105. Li, Y.C., He, Y.T. (2013) Anthocyanin Content and Antioxidant Activity of Different Varieties Blueberries. Advanced Materials Research 610,3421-3427.
    106. Muller, L., Riediker, M., Wick, P., Mohr, M., Gehr, P., Rothen-Rutishauser, B.(2010) Oxidative stress and inflammation response after nanoparticle exposure:differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways. Journal of the Royal Society Interface 7, S27-S40.
    107. Mohan, A., Narayanan, S., Sethuraman, S., Krishnan, U.M. (2013) Combinations of plant polyphenols & anti-cancer molecules:a novel treatment strategy for cancer chemotherapy. Anti-cancer agents in medicinal chemistry 13,281-295.
    108. Murapa, P., Dai, J., Chung, M., Mumper, R.J., D'Orazio, J. (2012) Anthocyanin-rich Fractions of Blackberry Extracts Reduce UV-induced Free Radicals and Oxidative Damage in Keratinocytes. Phytotherapy research 26,106-112.
    109.Noldin, V.F., Vigil, S.V., De Liz, R., Cechinel-Filho, V., Frode, T.S., Creczynski-Pasa, T.B. (2011) N-phenylmaleimide derivatives as mimetic agents of the pro-inflammatory process:myeloperoxidase activation. Pharmacological Reports 63,772-780.
    110. Raisuddin, S., Beigh, F. (2013) Ellagic acid protects against cyclophosphamide induced acute lung injury in Wistar rats by inhibiting oxidative stress, NF-kB activation and inflammatory cell production. Toxicology Letters 221, S107.
    111. Reuter, S., Gupta, S.C., Chaturvedi, M.M., Aggarwal, B.B. (2010) Oxidative stress, inflammation, and cancer:how are they linked? Free Radical Biology and Medicine 49,1603-1616.
    112. Suddek, G.M., Ashry, N.A., Gameil, N.M(2002)Thymoquinone attenuates cyclophosphamide-induced pulmonary injury in rats. Inflammopharmacology,1-9.
    113. Sulaiman, A.A., Hussain, S.A. (2012) Concentration and time dependent cytoprotective effects of anthocyanins against oxidative hemolysis induced by water and lipid soluble free radical initiators:an in vitro study. Oxidants and Antioxidants in Medical Science 1,133-140.
    114. Venkatesan, N., Chandrakasan, G (1995) Modulation of cyclophosphamide-induced early lung injury by curcumin, an anti-inflammatory antioxidant. Molecular and cellular biochemistry 142,79-87.
    115.王超颖,王洁(2009)常用抗肿瘤药物相关性肺损伤.中国肺癌杂志12.
    116.俞恒桑,楼亭,周丽,杨威,郭勇(2009)试述放化疗所致肺毒性的中西医治疗.实用中医药杂志25,257-258.
    117.关望,王海英,陈志芳,关岚,李天水,金红方,赵斌,杜军保(2010)外源性硫化氢对急性肺损伤大鼠氧化应激的调节作用.当代医学,7-8.
    118.张德玉,胡昕(2010)化疗药物的不良反应及护理.全科护理8,2387-2388.
    119.邓玲慧,陶敏(2012)常用抗肿瘤药物相关肺毒性.国际肿瘤学杂志ISTIC 39.
    120. Shanmugarajan T S, Arunsundar M, Somasundaram Ⅰ, et al. (2008) Cardioprotective effect of Ficus hispida Linn. on cyclophosphamide provoked oxidative myocardial injury in a rat model[J]. International Journal of Pharmacology,4(2):78-87.
    121. Basnakian, A. G, G P. Kaushal & S. V. Shah (2002) Apoptotic pathways of oxidative damage to renal tubular epithelial cells. Antioxidants and Redox Signaling,4,915-924.
    122. Chess-Williams, R., K. Mills & C. McDermott (2012) ACROLEIN, A METABOLITE OF CYCLOPHOSPHAMIDE ENHANCES BASAL ATP RELEASE AND REACTIVE OXYGEN SPECIES FORMATION IN CULTURED HUMAN UROTHELIAL CELLS. In NEUROUROLOGY AND URODYNAMICS,1019-1019. WILEY-BLACKWELL 111 RIVER ST, HOBOKEN 07030-5774, NJ USA.
    123. Cleland, B. & C. Pokorny (1993) Cyclophosphamide related hepatotoxicity. Australian and New Zealand journal of medicine,23,408.
    124. De Jonge, M. E., A. D. Huitema, S. Rodenhuis & J. H. Beijnen (2005) Clinical pharmacokinetics of cyclophosphamide. Clinical pharmacokinetics,44,1135-1164.
    125. GOLDBERG, J. W. & M. D. LIDSKY (1985) Cyclophosphamide-associated hepatotoxicity. Southern medical journal,78,222-223.
    126. He, F., C. Wu, Q. Tu & G Xing (1993) Human hepatic stimulator substance:a product of gene expression of human fetal liver tissue. Hepatology,17,225-229.
    127. Hijiya, N., B. Thomson, M. S. Isakoff, L. B. Silverman, P. G Steinherz, M. J. Borowitz, R. Kadota, T. Cooper, V. Shen & G Dahl (2011) Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. Blood,118,6043-6049.
    128. Hughes, F. M., A. G Corn, A. R. Nimmich, J. D. Pratt-Thomas & J. T. Purves (2013) Cyclophosphamide induces an early wave of acrolein-independent apoptosis in the urothelium.
    129. King, P. D. & M. C. Perry (2001) Hepatotoxicity of chemotherapy. The oncologist,6,162-176.
    130. Ma, B., W. Yeo, P. Hui, W. M. Ho & P. J. Johnson (2002) Acute toxicity of adjuvant doxorubicin and cyclophosphamide for early breast cancer-a retrospective review of Chinese patients and comparison with an historic Western series. Radiotherapy and oncology,62,185-189.
    131.Mehra, L., D. MacLean, R. Shewfelt, K. Smith & H. Scherm (2013) Effect of postharvest biofumigation on fungal decay, sensory quality, and antioxidant levels of blueberry fruit. Postharvest Biology and Technology,85,109-115.
    132. Mills, B. A. & R. W. Roberts (1979) Cyclophosphamide-induced cardiomyopathy. A report of two cases and review of the english literature. Cancer,43,2223-2226.
    133. Mills, K., C. McDermott & R. Chess-Williams (2013) CHLOROACETALDEHYDE, AND NOT ACROLEIN, IS THE MORE URO-TOXIC METABOLITE OF CYCLOPHOSPHAMIDE AND ISOFOSFAMIDE IN VITRO. In NEUROUROLOGY AND URODYNAMICS,724-725. WILEY-BLACKWELL 111 RIVER ST, HOBOKEN 07030-5774, NJ USA.
    134. Mok, C.-C., W.-M. Wong, T. W.-H. Shek, C. T.-K. Ho, C.-S. Lau & C.-L. Lai (2000) Cumulative hepatotoxicity induced by continuous low-dose cyclophosphamide therapy. The American journal of gastroenterology,95,845-846.
    135. Nafees, S., S. T. Ahmad, W. Arjumand, S. Rashid, N. Ali & S. Sultana (2012) Modulatory effects of gentisic acid against genotoxicity and hepatotoxicity induced by cyclophosphamide in Swiss albino mice. Journal of Pharmacy and Pharmacology,64,259-267.
    136. Petrik, J., T. Zanic-Grubisic, K. Barisic, S. Pepeljnjak, B. Radic, Z. Ferencic & I. Cepelak (2003) Apoptosis and oxidative stress induced by ochratoxin A in rat kidney. Archives of toxicology,77, 685-693.
    137. Senthilkumar, S., T. Devaki, B. M. Manohar & M. S. Babu (2006) Effect of squalene on cyclophosphamide-induced toxicity. Clinica chimica acta,364,335-342.
    138. SNYDER, L. S., R. I. HEIGH & M. L. ANDERSON (1993) Cyclophosphamide-induced hepatotoxicity in a patient with Wegener's granulomatosis. In Mayo Clinic Proceedings,1203-1204. Elsevier.
    139. Subramaniam, S. R., R. A. Cader, R. Mohd, K. W. Yen & H. A. Ghafor (2013) Low-dose cyclophosphamide-induced acute hepatotoxicity. The American journal of case reports,14,345.
    140. Sun, L.-Q., X.-P. Ding, J. Qi, H. Yu, S.-a. He, J. Zhang, H.-X. Ge & B.-Y. Yu (2012) Antioxidant anthocyanins screening through spectrum-effect relationships and DPPH-HPLC-DAD analysis on nine cultivars of introduced rabbiteye blueberry in China. Food Chemistry,132,759-765.
    141. Wang, S. Y, H. Chen, M. J. Camp & M. K. Ehlenfeldt (2012) Genotype and growing season influence blueberry antioxidant capacity and other quality attributes. International Journal of Food Science & Technology,47,1540-1549.
    142. Yao, S., W. E. Barlow, K. S. Albain, J.-Y. Choi, H. Zhao, R. B. Livingston, W. Davis, J. M. Rae, I.-T. Yeh & L. F. Hutchins (2010) Gene polymorphisms in cyclophosphamide metabolism pathway, treatment-related toxicity, and disease-free survival in SWOG 8897 clinical trial for breast cancer. Clinical Cancer Research,16,6169-6176.
    143. Yao, Z., W. Yang, W. Zhang, Y. Chen & Y. Zhou (1992) Hepatic stimulator substance from human fetal liver for treatment of experimental hepatic failure. Chinese medical journal,105,676.
    144.刁继红,刘佳,刘爽,刘男,张颖丽,杨绍群&张善玉(2011)金顶侧耳多糖对环磷酰胺中毒小鼠肝保护作用的实验研究.时珍国医国药,22,2296-2297.
    145.于洪升,吴刑,王卓敏&崔复宪(2007)低剂量辐射对环磷酰胺致肝功能损伤的影响.第四军医大学学报,28,574-575.
    146.李彩凤,许树根,蔡辉,胡玉清&梁萌(2009)还原型谷胱甘肽在环磷酰胺冲击治疗狼疮性肾炎中对肝脏的保护作用.临床军医杂志,37,1080-1080.
    147.梁冰,李淑芳,王骁宇,刘锦红&沈祥春(2012)氧化苦参碱对环磷酰胺增效减毒作用.中华中医药杂志,7,056.
    148.刘佳.2010.金顶侧耳质量评价方法及对环磷酰胺致小鼠肝毒性影响的研究.延边大学.
    149.Bagchi, D., A. Garg, R. Krohn, M. Bagchi, D. Bagchi, J. Balmoori & S. Stohs (1998) Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. General Pharmacology:The Vascular System,30,771-776.
    150. Bagchi, D., A. Garg, R. Krohn, M. Bagchi, M. Tran & S. Stohs (1997) Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Research Communications in Molecular Pathology and Pharmacology,95,179.
    151. Basson, A. B., S. E. Terblanche & W. Oelofsen (1982) A comparative study on the effects of ageing and training on the levels of lipofuscin in various tissues of the rat. Comparative Biochemistry and Physiology Part A:Physiology,71,369-374.
    152.孔庆胜,张向阳,宋爱芹,韩晓琳&刘玉庆(2005)大鼠学习记忆能力和特定脑区的抗氧化酶活性[J].中国临床康复,9,244-245.
    153.白雪,杨杰,刘昌福,宋玉莲&郝小燕(2008)延胡索总生物碱对D-半乳糖所致衰老模型小鼠相关指标的影响.贵州医药,32,399-401.
    154张熙&张荷樽(1996)D—半乳糖诱导拟衰老动物模型的记忆行为改变.中国老年学杂志,16,230-232.
    155.韩志涛,张炳烈,张京立,李文彬&陶国枢(2004)施普善对D-半乳糖拟衰老小鼠学习记忆功能的影响[J].中国临床康复,8,1846-1847.
    156.张龙翔,张庭芳,李令媛(1997)生物化学实验方法和技术.第二版.北京:高等教育出版社,20-23,100-106.
    157.秦红兵,杨朝晔,范忆江等(2009)D-半乳糖诱导衰老小鼠模型的建立与评价[J].中国组织工程研究与临床康复,13(7),1275-1278.
    158.赵永芳(1994)生物化学技术原理及其应用.第二版.武汉:武汉大学出版社.78-173,355-395.
    159.周加祥,刘铮(2000)生物分离技术与过程研究进展.化工进展.6:38-41
    160.周先碗,胡晓倩(2003)生物化学仪器分析与实验技术.北京:化学工业出版社.116-123.
    161.余资江,应大君,董世武等(2005).半乳糖急性致衰老动物模型剂量的探讨[J].解剖学杂志,28(4),423-429.
    162.徐俐,金毅,王斌,尹英(2006)树莓红色素的提取及稳定性的研究.食品科学,191-194
    163.许琛琦,秦德安(2001)SOD-GC脂质体的制备及包封率的测定.日用化学工业,31(1)12-16
    164.阎家麒,谢文正(1994)月桂酸修饰超氧化物歧化酶的制备及其性质研究.生物化学与生物物理进展,21(2):154-157
    165.杨保珍,张天民(1990)超氧化物歧化酶的化学修饰.中国医药工业杂志.21(11):519-523
    166.杨东升(2004)超氧化物歧化酶的研究与应用.化学与生物工程,21(3):7-9
    167.杨节非编译(1994)固定化酶—回顾与展望.国外医药,15(4):209-212
    168.王怀颖,张玮,石少慧等(2005).D-半乳糖老化模型小鼠抗氧化能力的实验研究[J].军医进修学院学报,26(5),397-400.
    169.曩潇潇,何瑶,王晓炜等(2004)富硒沼泽红假单胞菌对D-半乳糖致衰老小鼠抗氧化系统的影响[J].安徽农业科学,35(16),4850-4852.
    170.杨莉,杨萍,申虹等(2003)超氧化物岐化酶修饰前后的稳定性比较.郑州工程学院学报,24(1):68-70
    171.杨明琰,张晓琦等(2004)微生物产超氧化物歧化酶的研究进展.微生物学杂志,24(1):49-52
    172.禹邦超,文德立(1994)应用酶学导论.武汉:华中师范大学出版社

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