蚕丝蛋白肽对S180荷瘤小鼠免疫调节作用的研究

徐姗 杜双双 阎昭

徐姗, 杜双双, 阎昭. 蚕丝蛋白肽对S180荷瘤小鼠免疫调节作用的研究[J]. 中国肿瘤临床, 2021, 48(1): 1-7. doi: 10.3969/j.issn.1000-8179.2021.01.089
引用本文: 徐姗, 杜双双, 阎昭. 蚕丝蛋白肽对S180荷瘤小鼠免疫调节作用的研究[J]. 中国肿瘤临床, 2021, 48(1): 1-7. doi: 10.3969/j.issn.1000-8179.2021.01.089
Shan Xu, Shuangshuang Du, Zhao Yan. Immunoregulatory effect of silk fibroin peptide in S180 tumor-bearing mice[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2021, 48(1): 1-7. doi: 10.3969/j.issn.1000-8179.2021.01.089
Citation: Shan Xu, Shuangshuang Du, Zhao Yan. Immunoregulatory effect of silk fibroin peptide in S180 tumor-bearing mice[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2021, 48(1): 1-7. doi: 10.3969/j.issn.1000-8179.2021.01.089

蚕丝蛋白肽对S180荷瘤小鼠免疫调节作用的研究

doi: 10.3969/j.issn.1000-8179.2021.01.089
详细信息
    作者简介:

    徐姗  专业方向为临床药理学。E-mail:postgraduate_xs@163.com

    通讯作者:

    阎昭  yanzhaopaper@163.com

Immunoregulatory effect of silk fibroin peptide in S180 tumor-bearing mice

More Information
  • 摘要:   目的  探索蚕丝蛋白肽(silk fibroin peptide,SFP)在肿瘤环境下的免疫调节作用,为临床应用提供药理学基础。  方法  构建小鼠S180皮下移植瘤模型,分为空白对照组(生理盐水),阳性对照药胸腺五肽组(TP-5,1 mg/kg),蚕丝蛋白肽低剂量组(SFP-L,300 mg/kg)和蚕丝蛋白肽高剂量组(SFP-H,600 mg/kg),腹腔注射连续给药28天。初步评价SFP的抗肿瘤免疫作用;计算免疫脏器指数,评价SFP对于荷瘤小鼠免疫系统发育的影响;苏木精-伊红染色,观察肿瘤组织中的肿瘤浸润性淋巴细胞的数量及分布情况。荷瘤小鼠特异性免疫应答的评价通过流式细胞术测定IL-2、IL-4、IL-5、IFN-γ和TNF-α的分泌水平;MTT法测定T淋巴细胞的增殖能力并计算刺激指数;流式细胞术检测CD4+和CD8+T淋巴细胞亚群的比例;绵羊红细胞免疫小鼠,观察比较小鼠血清的抗体水平。非特异性免疫应答的评价则通过测定小鼠的碳粒廓清指数,衡量巨噬细胞的吞噬能力以及利用MTT法测定自然杀伤细胞的活力。  结果  SFP具有良好的抗肿瘤活性,可提高胸腺和脾脏的免疫脏器指数(P < 0.05),高剂量SFP可提高肿瘤组织淋巴细胞的浸润程度。在荷瘤小鼠的特异性免疫应答评价中,SFP可提高荷瘤小鼠血清中IL-2、IL-4和TNF-α的分泌水平以及淋巴细胞刺激指数,高剂量SFP可提高T淋巴细胞亚群的比例(P < 0.05);在非特异性免疫应答评价中,SFP可提高巨噬细胞的吞噬系数α值(P < 0.05)。  结论  SFP可保护荷瘤小鼠的免疫器官发育,促进肿瘤的局部免疫,还可通过上调特异性及非特异性免疫应答,完善荷瘤小鼠的免疫保护机制,促进荷瘤小鼠的抗肿瘤免疫应答。

     

  • 图  1  SFP的体内抗肿瘤活性及安全性评价

    A:给药期间小鼠肿瘤体积变化;B:抑瘤率;C:给药期间小鼠体质量变化;与空白对照组相比,*P < 0.05

    图  2  免疫器官脏器指数(x±sn=6)

    A:脾脏解剖图;B:脾脏指数;C:胸腺解剖图;D:胸腺指数;与空白对照组相比,*P < 0.05,**P < 0.01

    图  3  肿瘤浸润性淋巴细胞H & E染色结果

    图  4  细胞因子的分泌水平

    A:IL-2;B:IL-4;C:TNF-α;与空白对照组相比,*P < 0.05;与阳性对照药物TP-5相比,#P < 0.05

    图  5  CD4+及CD8+T淋巴细胞亚群分析及血清溶血素含量

    A:CD4+及CD8+T淋巴细胞亚群检测结果;B:CD4+及CD8+T淋巴细胞亚群定量分析;C:血清溶血素含量;与空白对照组相比,*P<0.05

    图  6  巨噬细胞和自然杀伤细胞的活性评价

    A:巨噬细胞的吞噬指数α;B:自然杀伤细胞活性;与空白对照组相比,**P < 0.01;与阳性对照药物TP-5相比,#P < 0.05

    表  1  淋巴细胞刺激指数(x±sn=6)

    表  2  CD4+和CD8+T淋巴细胞亚群的比例(x±sn=6)

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出版历程
  • 收稿日期:  2020-08-29
  • 刊出日期:  2021-01-15

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