首页|胀果甘草多糖佐助的树突状细胞疫苗对H22肝癌荷瘤小鼠的免疫治疗作用

胀果甘草多糖佐助的树突状细胞疫苗对H22肝癌荷瘤小鼠的免疫治疗作用

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目的:制备胀果甘草多糖佐助的树突状细胞(dendritic cell,DC)疫苗,研究其对H22肝癌荷瘤小鼠的免疫治疗作用。方法:从小鼠骨髓中分离培养得到骨髓源树突状细胞(bone marrow-derived dendritic cells,BMDC),用H22肝癌抗原致敏DC,再加入一定浓度的胀果甘草多糖佐剂制备DC疫苗,用倒置显微镜观察DC形态变化、流式细胞仪检测DC疫苗表型。建立H22肝癌荷瘤小鼠模型,按数字表法随机分为模型组、阳性组、DC组、TNF-α组、GiP组和GiP-B1组,用胀果甘草多糖佐助的DC疫苗免疫治疗荷瘤小鼠2次。末次给药后第5天处死小鼠,检测脏器指数及抑瘤率;酶联免疫法检测小鼠血清中IL-12(P70)、IFN-γ、IL-4和IL-10细胞因子含量;HE染色观察小鼠肝脏和肿瘤组织病理形态变化;免疫组化检测肿瘤组织Bax和Bcl-2蛋白的表达水平。结果:胀果甘草多糖作为DC疫苗佐剂,能够上调DC表面标志分子的表达水平(P<0。05);胀果甘草多糖佐助的DC疫苗能够减缓肝癌小鼠肿瘤生长速度,升高肝癌小鼠脾脏指数和胸腺指数(P<0。05),增加肝癌小鼠血清中IL-12和IFN-γ含量(P<0。05),降低IL-10和IL-4含量(P<0。05),提高肿瘤组织Bax/Bcl-2比值(P<0。01)。结论:胀果甘草多糖作为DC疫苗的佐剂,可以体外诱导DC成熟及活化,胀果甘草多糖佐助的DC疫苗对肝癌小鼠具有一定的免疫治疗作用,其抗肿瘤作用机制可能与促进DC成熟增加IL-12和IFN-γ的分泌,介导细胞免疫,并促进肿瘤细胞凋亡有关。
Immunotherapeutic effect of dendritic cell vaccine assisted by Glycyrrhiza inflata polysaccharides in H22 hepatoma-bearing mice
OBJECTIVE To prepare dendritic cell(DC)vaccine assisted by Glycyrrhiza inflata polysaccharide and to study its immunotherapeutic effect in H22 hepatoma-bearing mice.METHODS Bone marrow-derived dendritic cells(BMDC)were isolated from mouse bone marrow and cultured,DC was sensitized with H22 hepatoma antigen,and then a certain concentration of Glycyrrhiza inflata polysaccharides adjuvant was added to prepare DC vaccine.The morphological changes of DC were observed under an inverted microscope,and the phenotype of DC vaccine was detected by flow cytometry.H22 hepatoma-bearing mice was established and randomly divided into model group,positive group,DC group,TNF-α group,GiP group and GiP-B1 group by digital table method.The tumor-bearing mice were immunized with DC vaccine assisted by Glycyrrhiza inflata polysac-charides.The mice were sacrificed on the fifth day after the last administration,and the organ index and tumor inhibition rate were detected.The contents of IL-12(P70),IFN-γ,IL-4 and IL-10 cytokines in serum were detected by enzyme linked immunosor-bent assay(ELISA).The pathomorphological changes of liver and tumor tissue were observed by HE staining,and the expres-sion levels of Bax and Bcl-2 protein in tumor tissue were detected by immune-histochemistry.RESULTS Glycyrrhiza inflata polysaccharides as an adjuvant of DC vaccine could up-regulate the expression of DC surface markers(P<0.05).The DC vaccine assisted by Glycyrrhiza inflata polysaccharides could slow down the tumor growth rate in tumor-bearing mice,increase the spleen index and thymus index of tumor-bearing mice(P<0.05),increase the contents of IL-12 and IFN-γ in serum of tumor-bearing mice(P<0.05),decrease the contents of IL-10 and IL-4(P<0.05),and increase the ratio of Bax/Bcl-2 in tumor tissue(P<0.01).CONCLUSION Glycyrrhiza inflata polysaccharide,as an adjuvant of DC vaccine,can induce DC maturation and activa-tion in vitro,and has a certain immunotherapeutic effect in tumor-bearing mice.Its anti-tumor mechanism may be related to up-regulating the secretion of IL-12 and IFN-γ,mediating cellular immunity and promoting tumor cell apoptosis.

Glycyrrhiza inflata polysaccharidesdendritic cellsdendritic cell vaccineimmunotherapyanti-tumor effect

俞永婷、娜迪热木·肖克拉提、卢泳强、周朝曦、丛媛媛

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新疆医科大学药学院,新疆乌鲁木齐 830011

胀果甘草多糖 树突状细胞 树突状细胞疫苗 免疫治疗 抗肿瘤作用

国家自然科学基金新疆天然药物活性组分与释药技术重点实验室项目

81960702XJDX1713

2024

中国医院药学杂志
中国药学会

中国医院药学杂志

CSTPCD北大核心
影响因子:1.198
ISSN:1001-5213
年,卷(期):2024.44(1)
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