硒化卡拉胶联合表阿霉素体内对H_(22)肝癌小鼠抗肿瘤与抗氧化作用的研究
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摘要
目的通过体内抗肿瘤试验,研究硒化卡拉胶(KSC)联合表阿霉素(EPI)对H_(22)肝癌移植瘤生长的抑制及抗氧化作用。方法将H_(22)移植性肝癌小鼠随机分为8组,每组10只,治疗期间考察各组小鼠的体重变化及生存状态。停药次日,对脾指数、胸腺指数、抑瘤率进行测定,并检测血清中GSH-Px、SOD、CAT活性及GSH、MDA的含量变化。结果 KSC单独及联合EPI可改善H_(22)小鼠的免疫器官指数,提高抑瘤率;与模型对照组相比,中、高剂量KSC可显著提高GSH-Px、CAT活性及GSH含量(P<0.05),高剂量KSC可显著提高SOD活性(P<0.01),同时各EPI组GSH-Px、SOD、CAT活性均显著降低(P<0.05),而MDA显著增高(P<0.01);中、高剂量KSC联合EPI可使GSH-Px、SOD、CAT活性均显著恢复(P<0.05),而MDA含量显著降低(P<0.01)。结论硒化卡拉胶具有良好的免疫调节和抗氧化作用,联合用药可显著改善表阿霉素的毒副作用,提高机体抗氧化水平,对治疗小鼠移植性肝癌有显著的增效作用。
Objective To study the effects of Kappa-Selenocarrageenan(KSC)with epirubicin(EPI)on growth inhibition and anti-oxidation of mice with hepatoma H_(22).Methods H_(22) hepatoma mice were randomly divided into eight groups and each group had ten mice.Weight change and living condition were investigated during the administration period.The spleen index,thymus index,inhibitory rate and serum GSH-Px,SOD,CAT,GSH,MDA were examined on the next day of drug discontinuance.Results KSC alone or in combination with epirubicin could improve the immune organ index of hepatoma mice and the inhibitory rate.Compared with the control group,middle-and high-dose KSC could significantly increase GSH-Px and CAT activity and GSH content(P<0.05),high-dose KSC could substantially increase the SOD activities(P<0.01).Meanwhile,the GSH-Px,SOD,CAT activities of epirubicin group were lower(P<0.05)whereas MDA increased(P<0.01)in epirubicin groups.Middle-and high-dose KSC combined with epirubicin could make the GSH-Px,SOD,CAT activity obviously regained(P<0.05),and MDA content highly decreased(P<0.01).Conclusion KSC showed excellent effect on immunity and anti-oxidation,the combination therapy could reduce the toxic effects of epirubicin and enhance the antioxidant levels.KSC had significantly synergistic effect on the treatment of hepatoma H_(22).
Objective To study the effects of Kappa-Selenocarrageenan(KSC)with epirubicin(EPI)on growth inhibition and anti-oxidation of mice with hepatoma H_(22).Methods H_(22) hepatoma mice were randomly divided into eight groups and each group had ten mice.Weight change and living condition were investigated during the administration period.The spleen index,thymus index,inhibitory rate and serum GSH-Px,SOD,CAT,GSH,MDA were examined on the next day of drug discontinuance.Results KSC alone or in combination with epirubicin could improve the immune organ index of hepatoma mice and the inhibitory rate.Compared with the control group,middle-and high-dose KSC could significantly increase GSH-Px and CAT activity and GSH content(P<0.05),high-dose KSC could substantially increase the SOD activities(P<0.01).Meanwhile,the GSH-Px,SOD,CAT activities of epirubicin group were lower(P<0.05)whereas MDA increased(P<0.01)in epirubicin groups.Middle-and high-dose KSC combined with epirubicin could make the GSH-Px,SOD,CAT activity obviously regained(P<0.05),and MDA content highly decreased(P<0.01).Conclusion KSC showed excellent effect on immunity and anti-oxidation,the combination therapy could reduce the toxic effects of epirubicin and enhance the antioxidant levels.KSC had significantly synergistic effect on the treatment of hepatoma H_(22).
引文
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[15]张连龙,戴敏,毛兆祥,等.灵芝多糖/硒化卡拉胶口服液对免疫抑制小鼠免疫功能的影响[J].中国临床药理学与治疗学,2008,13(12):1381-1387.
[16]林显敢,谢德荣,梁新文,等.硒制剂在预防化疗过程中血液毒性的作用[J].微量元素与健康研究,2001,18(2):23-24.
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[18]来小丹,冉启文,欧阳净,等.P53介导的活性氧通路对硒酸酯多糖诱导骨肉瘤细胞凋亡的作用[J].中国药业,2015,24(21):103-105.
[19]陈晋,陈家强,罗斌,等.硒对胃癌化疗敏感性影响的研究进展[J].预防医学情报杂志,2013,29(8):719-722.
[2]Den Brok M H,Nierkens S,Figdor C G,et al.Dendritic cells:tools and targets for antitumor vaccination.Expert Rev Vaccines,2005,4(5):699-710.
[3]Tao M,Kruhlak M,Xia S,et al.Signals that dictate nuclear localization of human papillomavirus type 16oncoprotein E6in living cells[J].J Virol,2003,77(24):13232-13247.
[4]张哲文,魏虎来,苏海翔.硒酸酯多糖的免疫调节与抗肿瘤作用[J].兰州大学学报(医学版),2005,31(2):88-91.
[5]凌娜,孙庆岩,徐艳艳,等.硒化卡拉胶联合表阿霉素对肝癌HepG-2细胞增殖及细胞周期的影响[J].食品与药品,2014,16(2):81-84.
[6]王佳艺,何俊劲,郝静超,等.多肽AP25与多西他赛联合用药对人乳腺癌裸鼠移植癌的抑制活性研究[J].中国药理学通报,2015,31(9):1233-1238.
[7]高军,祝小英,石庆芳,等.沙利度胺联合表阿霉素对小鼠H22肝癌移植瘤的生长抑制研究[J].中国临床药理学杂志,2016,32(2):170-173.
[8]史沛,茹凤娟,赵毅,等.原发性肝癌介入治疗的疗效观察[J].中国实用医药,2013,8(17):91-92.
[9]Oddens J R,Sylvester R J,Brausi M A,et al.The effect of age on the efficacy of maintenance bacillus calmette guerin relative to maintenance epirubicin in patients with stage Ta T1urothelial bladder cancer:results from EORTC GenitoUrinary Group Study 30911[J].Eur Urol,2014,66(4):694-701.
[10]Petit T.Anthracycline-induced cardiotoxicity.Bull Cancer,2004,91Suppl 3:159-165.
[11]阎兵,王学东,谭斌,等.不同硒源对小鼠抗氧化、免疫及组织硒贮存影响的研究[J].粮食科技与经济,2011,36(2):46-48.
[12]张华,黄克和,薛家宾,等.不同硒源对兔体液免疫及抗氧化能力影响的研究[J].营养学报,2006,28(3):209-212.
[13]张善玉,朴娟玉,宛莹,等.不同给药次数环磷酰胺诱导小鼠肝损伤的对比研究[J].延边大学医学学报,2009,32(1):22-25.
[14]王黎,裴瑞,杨红梅,等.顺铂诱导肾损伤过程中肾皮质脂质过氧化的变化[J].中国应用生理学杂志,2004,20(4):82-84.
[15]张连龙,戴敏,毛兆祥,等.灵芝多糖/硒化卡拉胶口服液对免疫抑制小鼠免疫功能的影响[J].中国临床药理学与治疗学,2008,13(12):1381-1387.
[16]林显敢,谢德荣,梁新文,等.硒制剂在预防化疗过程中血液毒性的作用[J].微量元素与健康研究,2001,18(2):23-24.
[17]吴海歌.硒化卡拉胶寡糖的制备及其抑制血管生成作用研究[J].化学与生物工程,2014,31(9):13-16.
[18]来小丹,冉启文,欧阳净,等.P53介导的活性氧通路对硒酸酯多糖诱导骨肉瘤细胞凋亡的作用[J].中国药业,2015,24(21):103-105.
[19]陈晋,陈家强,罗斌,等.硒对胃癌化疗敏感性影响的研究进展[J].预防医学情报杂志,2013,29(8):719-722.