寡糖亚硒酸酯的抗肿瘤活性研究
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摘要
寡糖具有提高机体免疫力、抗肿瘤、促进有益菌繁殖等生物学功能,是当前研究热点之一。近年来,硒多糖作为抗肿瘤药物的研究已经比较多,而寡糖亚硒酸酯的抗肿瘤作用却很少报道。
本实验主要合成寡糖亚硒酸酯,并测定了其含硒量。从酯化工艺、反应条件方面加以改进,合成了性质稳定的寡糖亚硒酸酯。实验结果显示,其含硒量高,超过15%,且水溶性好并通过紫外、红外光谱学对产物结构进行了分析和鉴定。
在生物学方面,采用Ames试验,测试了寡糖亚硒酸酯的抗诱变活性,并研究了其对体外培养的宫颈癌细胞(HeLa)的影响,结果显示,蔗糖亚硒酸酯和棉籽糖亚硒酸酯对宫颈癌细胞都具有显著的抑制作用,且比亚硒酸钠的效果要好。另外,还对寡糖亚硒酸酯进行了动物活体实验,测试了小鼠肉瘤S180实体肿瘤的抑制率和对小鼠HeLa实体瘤的生命延长率测试,以及动物营养测试、急毒性测试。数据显示,蔗糖亚硒酸酯的灌胃给药剂量为40mg/kg·d时,其实体肿瘤的抑制率达到87%,当腹腔注射剂量为1mg/kg·d时,生命可延长一倍以上;棉籽糖亚硒酸酯的口服半致死量最高可达335mg/kg,当腹腔注射剂量为2mg/kg·d时,也可使荷瘤小鼠的生命延长一倍以上。
Oligosaccharide show a variety of biological activities, such as antitumor, and they can improve the body's antioxidation, and so on. So we pay more and more attention on oligosaccharide. Recently, many polysaccharide sulfates have been researched as antitumor drugs, while oligosaccharide selenite is several mentioned.
Oligosaccharide selenite was prepared and studied. We synthesized by changing reaction condition and improving synthesis technology. Two selenite compounds are stabilized, hydrosoluble and high Se content. And their structure was determined by IR spectrometer and UV spectrometer.
With regard to their biological activities, in Ames Test, oligosaccharide selenite could evidently inhibit the reverse mutation on Salmonella thphimurium strains TA98 with S9 mix. We also studied their effects on HeLa cell. The results show that both bucrose selenite and raffinose selenite are better than sodium selenite in inhibition. In addition, we also have a living animal experiment to oligosaccharide selenite, such as tumor inhibition, life extending, animal nutrition, acute- toxicity.
本实验主要合成寡糖亚硒酸酯,并测定了其含硒量。从酯化工艺、反应条件方面加以改进,合成了性质稳定的寡糖亚硒酸酯。实验结果显示,其含硒量高,超过15%,且水溶性好并通过紫外、红外光谱学对产物结构进行了分析和鉴定。
在生物学方面,采用Ames试验,测试了寡糖亚硒酸酯的抗诱变活性,并研究了其对体外培养的宫颈癌细胞(HeLa)的影响,结果显示,蔗糖亚硒酸酯和棉籽糖亚硒酸酯对宫颈癌细胞都具有显著的抑制作用,且比亚硒酸钠的效果要好。另外,还对寡糖亚硒酸酯进行了动物活体实验,测试了小鼠肉瘤S180实体肿瘤的抑制率和对小鼠HeLa实体瘤的生命延长率测试,以及动物营养测试、急毒性测试。数据显示,蔗糖亚硒酸酯的灌胃给药剂量为40mg/kg·d时,其实体肿瘤的抑制率达到87%,当腹腔注射剂量为1mg/kg·d时,生命可延长一倍以上;棉籽糖亚硒酸酯的口服半致死量最高可达335mg/kg,当腹腔注射剂量为2mg/kg·d时,也可使荷瘤小鼠的生命延长一倍以上。
Oligosaccharide show a variety of biological activities, such as antitumor, and they can improve the body's antioxidation, and so on. So we pay more and more attention on oligosaccharide. Recently, many polysaccharide sulfates have been researched as antitumor drugs, while oligosaccharide selenite is several mentioned.
Oligosaccharide selenite was prepared and studied. We synthesized by changing reaction condition and improving synthesis technology. Two selenite compounds are stabilized, hydrosoluble and high Se content. And their structure was determined by IR spectrometer and UV spectrometer.
With regard to their biological activities, in Ames Test, oligosaccharide selenite could evidently inhibit the reverse mutation on Salmonella thphimurium strains TA98 with S9 mix. We also studied their effects on HeLa cell. The results show that both bucrose selenite and raffinose selenite are better than sodium selenite in inhibition. In addition, we also have a living animal experiment to oligosaccharide selenite, such as tumor inhibition, life extending, animal nutrition, acute- toxicity.
引文
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[5]张俊杰.硒的生理功能及富硒强化食品的研究进展.微量元素与健康研究.2006,23(3):58-60.
[6]仝宗喜等.硒及硒蛋白生物学作用的研究进展.动物医学进展.2002,23(6):17-19.
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[10]郭利等.含硒化合物研究进展.中国新药杂志.2000,9(3):155-158.
[11]崔春兰,郝生宏,郑虎哲.微量元素硒的生物学功能.畜牧与饲料科学.2006,27(3):18-21.
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[13]谢忠忱.动物硒蛋白研究现状.中国饲料.2002,21(1):46-47.
[14]张笑天,熊永民.硫氧还蛋白还原酶研究进展.国外医学.2005,26(4):78-81.
[15]徐芳.硒的化学形态与生物形态分析的新技术和新方法.复旦大学博士论文.2003,4.
[16]和红.硒蛋白P的分子生物学进展.国外医学-医学地理分册.1996,17(1):1-3.
[17]董文甫,李艳红,岳文斌.哺乳动物硒蛋白的研究进展.中国畜牧兽医.2007,34(1):36-38.
[18]徐芳,邱德仁,杨芃原.硒蛋白的形态分析.化学世界.2006,4:44-45.
[19]鲁建国,王青,马庆久,宁力,房青,褚延魁等.硒蛋白P在结肠癌组织中的表达及其意义.第四军医大学学报.2006,27(14):19-23.
[20]梁润梅.硒蛋白及其生物学功能.生物学教学.2004,29(9):8-11.
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[23]陈昕,薛德平,傅辛福,李吉学.微量元素硒的生理功能.南京军医学院学报.2000,22(2):103-104.
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[25]孙长峰,郭娜.微量元素硒的生理功能.微量元素与健康研究.2007,24(6):67-68.
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