乌头碱联合聚肌胞苷酸免疫抑瘤机制及减毒作用  

Exploration into the immune mechanism and detoxication of aconitine combined with polycytidylic acid on antitumor

作　　者：韦志荣 王文佳 王苏杰 魏勤[3] 杨凤鸽 张蕊 李青[1] WEI Zhi-rong;WANG Wen-jia;WANG Su-jie;WEI Qin;YANG Feng-ge;ZHANG Rui;LI Qing(School of Basic Medical Sciences,Lanzhou University,Lanzhou 730000,China;Clinical Lab,Gansu Maternal and Child Health Hospital,Lanzhou 730050,China;Clinical Lab,Gansu Provincial People's Hospital,Lanzhou 730000,China;Internal Medicine Department,Haining Picheng Rehabilitation Hospital,Jiaxing 314400,Zhejiang,China;Clinical Lab,Gansu Provincial Cancer Hospital,Lanzhou 730050,China)

机构地区：[1]兰州大学基础医学院,兰州730000 [2]甘肃省妇幼保健院检验科,兰州730050 [3]甘肃省人民医院检验科,兰州730000 [4]海宁皮城康复医院内科,浙江嘉兴314400 [5]甘肃省肿瘤医院检验科,兰州730050

出　　处：《兰州大学学报（自然科学版）》2023年第2期248-255,共8页Journal of Lanzhou University(Natural Sciences)

基　　金：甘肃省重点研发计划项目(18YF1FA107,21YF5FA108)。

摘　　要：拟筛选出与聚肌胞苷酸(PolyIC)联合应用的附子有效剂型及给药方式,用于抗肿瘤治疗,初探其抑瘤免疫机制及PolyIC对附子有效成分的减毒效应.应用附子不同层次剂型,水煎剂、总生物碱及乌头碱纯品,分别联合PolyIC灌胃或腹腔给药移植瘤小鼠,测抑瘤率,苏木精-伊红染色法染色分析坏死面积,酶联免疫吸附测定血清干扰素,噻唑蓝、流式细胞术分别测脾脏淋巴细胞相对活性、T细胞亚型及细胞毒T淋巴细胞相关抗原4(CTLA4)表达;再选抑瘤最佳的药物测其毒性,乌头碱单倍剂量每日给药联合PolyIC隔日给药(非同步)、或乌头碱双倍剂量联合PolyIC均隔日给药(同步),测体重、血清酶、器官指数及存活率.结果显示,单独用药组、乌头碱灌胃联合组抑瘤率低于阳性对照,其余4个联合组与其无差异,其中乌头碱腹腔联合组抑瘤率最高为59.12%±19.64%,且仅该组肿瘤坏死面积大于阳性对照;其血清干扰素α(IFN-α)、干扰素(IFN-),脾脏淋巴细胞活性、分化决定簇抗原3、分化决定簇抗原4、分化决定簇抗原8(CD8*)T细胞百分比高于未治疗组,CD8^(+)T细胞CTLA4表达降低.乌头碱与PolyIC同步给药组体重高于非同步组,其存活率与未治疗及PolyIC组无差异,乌头碱组小鼠均死亡,提示乌头碱腹腔注射联合PolyIC抑瘤效果最佳,机制与IFN-α、IFN-分泌及T细胞抗肿瘤免疫有关;PolyIC可减毒乌头碱,两者同步给药减毒效果更佳.Aconite alkaloids and delivery methods were screened out and combined with polycytidylic acid(PolyIC)to explore the antitumor and the immune mechanism of antitumor and the detoxication of PolyIC on aconite.Several reagent types of aconite and its alkaloid combined with PolylC were used to orally or intraperitoneally administer to allograft mice.The tumor inhibition rate,necrotic area and serum interferon were measured via hematoxylin-eosin staining and enzyme linked immunosorbent assay.The relative activity of lymphocytes,subtypes and CTLA4(cytotoxic T lymphocyte-associated antigen-4)expression on T cells were analyzed via methyl thiazolyl tetrazolium and flow cytometry for mice spleen.Body weight,serum enzyme,organ index and survival rate were measured for toxicity detection on drug with the best inhibition,after the mice was administrated by a daily single dose of aconitine combined with PolyIC every other day(asynchronous)or double dose combined with PolyIC every other day(synchronous).No difference was found the in tumor inhibition rate for 4 combination groups except that it was lower for the aconitine intragastric combination and the groups'drug alone than the positive control;the tumor inhibition rate was the highest in the aconitine intraperitoneal combination only with a larger tumor necrosis area than the group positive control.Serum interferon-α(IFN-a)and interferon-(IFN-)increased similar as lymphocyte activity and percentage of cluster of differentiation 3t,cluster of differentiation 4^(+)and cluster of differentiation 8^(+)T cells in spleen.For the synchronous group,the body weight was higher than the asynchronous group,and there was no difference in the survival rate from the untreated or PolyIC groups.The mice died with aconitine alone.Intraperitoneal injection of aconitine combined with PolyIC had the best antitumor effect,underlying which the mechanism was related to an up-regulation of anti-tumor immunity on IFN-α,IFN-and T cells.PolyIC could detoxify aconitine,especial synchronous administra

关 键 词：附子生物碱 乌头碱 聚肌胞苷酸 肿瘤 TOLL样受体3 

分 类 号：R310.21[医药卫生—基础医学] R310.34