地龙胶囊及其主成分对小鼠移植瘤S180辐射增敏的研究  

Study on the radiosensitizing effect of Dilong Capsules and its main components in S180 sarcoma-bearing mice

作　　者：何悦 肖会敏 康晓刚 李玙 郭军 李豫蓉 HE Yue;XIAO Huimin;KANG Xiaogang;LI Yu;GUO Jun;LI Yurong(Department of Chinese Materia Medica and Natural Medicines,Air Force Medical University,Xi′an 710032,China;Shaanxi Hanguang Biotechnology Limited Company,Xi′an 710032,China;Department of Neurology,Xijing Hospital,Air Force Military Medical University,Xi′an 710032,China;Dean′s Office,Air Force Military Medical University,Xi′an 710032,China;Department of Radiology,Stomatological Hospital,Air Force Medical University,Xi′an 710032,China;Department of Military Preventive Medicine,Air Force Medical University,Xi′an 710032,China)

机构地区：[1]空军军医大学中药与天然药物教研室,西安710032 [2]陕西含光生物科技有限公司,西安710032 [3]空军军医大学西京医院神经内科,西安710032 [4]空军军医大学教务处,西安710032 [5]空军军医大学口腔医院影像医学科,西安710032 [6]空军军医大学军事预防医学系,西安710032

出　　处：《西北药学杂志》2019年第5期622-628,共7页Northwest Pharmaceutical Journal

基　　金：陕西省重点研发计划项目(编号:2017SF-296)

摘　　要：目的观察地龙胶囊(DLC)及其主成分(MC,由尿嘧啶、次黄嘌呤、黄嘌呤、肌苷、鸟苷、色氨酸、尿嘧啶核苷、2′-脱氧肌苷和2′-脱氧鸟苷等组成)的体内抗肿瘤活性,探讨其体内抑瘤作用机制。方法①取DLC低、中和高剂量组以及MC1、MC2和MC3,对小鼠S 180肉瘤细胞实体瘤模型进行体内抑瘤及合用60 Co-γ射线放射增效实验,测定肿瘤质量、脾脏与胸腺质量等的变化,计算抑瘤率、脾脏指数、胸腺指数,检测肿瘤中Bax和Bcl-2蛋白表达及小鼠血清肿瘤坏死因子-α(TNF-α)的含量变化;②通过对荷瘤小鼠单核细胞吞噬系统(RES)进行实验,计算吞噬指数K及吞噬系数α对荷瘤小鼠迟发性免疫反应的实验,计算抑瘤率、脾脏指数和胸腺指数。结果①DLC低、中和高剂量组以及MC1、MC2和MC3组对小鼠S 180肉瘤的抑瘤率分别为36.32%,45.06%,52.03%,36.11%,36.26%和45.08%;合用放疗(RT)抑瘤率分别为64.6%,69.4%,73.3%,62.7%,62.4%和68.6%;②DLC高、中、低剂量组以及MC1、MC2和MC3组小鼠的吞噬指数K及吞噬系数α均显著增加,能有效提高荷瘤小鼠细胞免疫的水平;③DLC中、高剂量组和MC3组肿瘤组织中Bcl-2阳性表达低于模型组,而Bax阳性表达高于模型组;RT+DLC 3个剂量组以及RT+MC3组肿瘤组织中Bcl-2阳性表达显著低于模型组,而Bax阳性表达显著高于模型组;④DLC中、高剂量组以及RT+MC3组小鼠血清中TNF-α的含量大于模型组,5-Fu可增加荷瘤小鼠血清TNF-α含量,小于DLC高剂量组;RT+DLC中、高剂量组以及RT+MC3组小鼠血清中TNF-α的含量大于模型对照组,5-Fu组可增加荷瘤小鼠血清TNF-α的含量,小于DLC高剂量组。结论DLC、MC1、MC2与MC3对小鼠S 180肉瘤的生长有明显的抑制作用,具有放射增敏效应,同时说明MC1、MC2和MC3可能是DLC的主要功效成分,其作用机制可能与免疫调节、促进TNF-α产生及调节Bcl-2/Bax凋亡通路有关。Objective To observe the antitumor activity of Dilong Capsules(DLC)and its main components(MC,consists of uracil,hypoxanthine,xanthine,inosine,guanosine,tryptophan,uracil nucleoside,2′-deoxyinosine and 2′-deoxyguanosine,etc.)and explore the mechanism of its antitumor effect in vivo.Methods①DLC(low,middle and high dose)groups and main components(MC1,MC2,MC3)groups were used to inhibit the tumor model of S 180 cancer cells in mice in vivo and 60 Co-γirradiation was used to synergize the tumor.The change weights of tumor mass,spleen and thymus were measured,and the inhibition rate,spleen index and thymus index were calculated.The expression of Bax and Bcl-2 in tumor and the change of serum TNF-αwere detected.②The phagocytic index K and phagocytic coefficientαwere calculated by the experiment of mononuclear phagocytic system(RES)in tumor-bearing mice,and the inhibition rate,spleen index and thymus index were calculated by the experiment of delayed immune response in tumor-bearing mice.Results①The mice′S 180 sarcoma inhibition rates of DLC low,middle and high doses groups,MC1,MC2 and MC3 groups were 36.32%,45.06%,52.03%,36.11%,36.26%and 45.08%,respectively,and 64.6%,69.4%,73.3%,62.7%,62.4%and 68.6%,respectively,with radiotherapy(RT).②DLC(low,middle and high dose),MC1,MC2 and MC3 groups can significantly enhance the phagocytic index K and phagocytic coefficientαof mice.DLC,MC1,MC2,MC3 can effectively improve the level of cellular immunity in tumor-bearing mice.③Bax positive expression in tumor tissues of DLC of middle,high dose group and MC3 group was significantly higher than that of model group,while Bcl-2 positive expression was significantly lower than that of model group.Bax positive expression in tumor tissues of RT+DLC of low,middle,high dose groups and RT+MC3 group was significantly higher than that of model group,while Bcl-2 positive expression was significantly lower than that of model group.④The contents of TNF-αin the serum of mice in DLC middle,high dose group,MC3 group were signific

关 键 词：地龙胶囊 辐射增敏 抗癌药物 肿瘤 S 180 尿嘧啶 核苷酸 

分 类 号：R965[医药卫生—药理学]