白英总甾体生物碱有效部位对体内肿瘤抑制及体外免疫调节作用研究  

Effect of the effective parts of total steroidal alkaloids from Solanum lyratum on tumor inhibition in vivo and immune regulation in vitro

作　　者：吴桐 王建农[1] 杜肖 WU Tong;WANG Jian-nong;DU Xiao(Beijing Key Laboratory of Chinese Materia Pharmacology,Institute ofBasic Medical Sciences,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091)

机构地区：[1]中国中医科学院西苑医院基础医学研究所/中药药理北京市重点实验室,北京100091

出　　处：《中南药学》2020年第11期1786-1790,共5页Central South Pharmacy

基　　金：国家自然科学基金面上项目(No.81872989);北京市自然科学基金面上项目(No.7102137);国家重大新药创制(No.2009ZX09103402);北京市科学技术委员会G20工程支撑保障-十病十药研发(No.Z151100003815026)。

摘　　要：目的研究白英总甾体生物碱(TAS)及其大极性和小极性部位对S180荷瘤小鼠体内抑瘤作用以及TAS对正常小鼠体外免疫调节作用。方法建立S180荷瘤小鼠模型,考察TAS大极性部位(TASG)和小极性部位(TASS)对荷瘤小鼠的抑瘤作用,以50、100、200 mg·kg^-1作为低(L)、中(M)、高(H)剂量组,另以TAS和环磷酰胺(CTX)作为阳性对照组,连续灌胃给药10 d。测定荷瘤小鼠的胸腺指数和脾脏指数,ELISA法检测TAS组荷瘤小鼠血清细胞因子IL-6、TGF-β和IFN-γ的水平,考察TAS体内抗肿瘤活性及免疫调节作用。体外采用CCK-8法检测TAS对T淋巴细胞、B淋巴细胞和腹腔巨噬细胞增殖能力的影响,中性红法检测巨噬细胞的吞噬能力,考察TAS对3种免疫细胞的调节作用。结果 TASS-L组、TASG-H组和TAS组的抑瘤率较高,分别为39.71%、43.92% 和42.13%;与模型组相比,CTX组S180荷瘤小鼠的胸腺指数和脾脏指数均显著降低(P<0.01),TAS各给药组,除TASG-H组外,动物的脾脏指数均明显升高,其中TASS-L和TASS-H组动物脾脏指数显著升高(P<0.01或P<0.05);与CTX组相比,TASS-M、TASS-H和TASG-H组荷瘤小鼠的胸腺指数及TAS各给药组动物的脾脏指数均显著升高;与模型组和CTX组相比,TAS组荷瘤动物血清中的IFN-γ水平显著升高(P<0.05)。体外免疫实验结果显示,在低浓度下,TAS能够显著促进T淋巴细胞、B淋巴细胞和腹腔巨噬细胞增殖,并增强巨噬细胞的吞噬能力(P<0.001),且浓度越小作用越明显,浓度增大则表现为明显的抑制作用(P<0.001)。结论 TAS及其大极性和小极性部位均可抑制小鼠S180移植瘤的生长,且具有增强荷瘤小鼠免疫功能的作用;此外,TAS可能具有双向免疫调节作用。Objective To determine the anti-tumor effect of total steroidal alkaloids from Solanum lyratum (TAS) and its large and small polar parts on S180 tumor-bearing mice in vivo and the immunoregulatory effect of TAS on normal mice in vitro.Methods S180 tumor-bearing mouse model was established to investigate the anti-tumor effect of TAS large polar part (TASG) and small polar part (TASS) on the tumor-bearing mice.Three dose group at 50,100,and 200 mg·kg^-1 as low (L),medium (M),and high (H) were set up;TAS and cyclophosphamide (CTX) were used as the positive control groups.The anti-tumor activity and immunomodulatory effect of TAS in vivo were evaluated by measuring the thymus and spleen indexes in the tumor-bearing mice.ELISA was used detect the levels of serum cytokines IL-6,TGF-β,and IFN-γ in the tumor-bearing mice of the TAS group.In vitro,CCK-8 assay was used to detect the proliferation of TAS on T and B lymphocytes and peritoneal macrophages,and neutral red assay was used to detect the phagocytosis of the macrophages,to investigate the immunomodulatory activities of TAS on the three immune cells.Results The tumor inhibition rate was 39.71% in the TASS-L group,43.92% in the TASG-H group,and 42.13% in the TAS group,respectively.Compared with those of the model group,the thymus and spleen indices of the S180 tumor-bearing mice in the CTX group were significantly reduced (P<0.01).The spleen index of the mice in each group of alkaloids from Solanum lyratum was all increased significantly,especially in the TASS-L and TASS-H groups (P < 0.01 or P < 0.05),Compared with that of the CTX group,the thymus index of the spleen-bearing mice in the TASS-M,TASS-H,and TASG-H groups the spleen index of the mice in each group was significantly increased.Compared with those of the model group and the CTX group,the levels of IFN-γ in the serum of the tumor-bearing mice in the TAS group were significantly increased (P<0.05).The in vitro immunity experiments showed that TAS facilitated the proliferation of T and B lymphocytes and t

关 键 词：白英 甾体糖苷生物碱 极性部位 抗肿瘤作用 免疫调节活性 

分 类 号：R285[医药卫生—中药学]