雪上一枝蒿多糖调控调节性T细胞抑制肝癌肺转移机制的研究

Polysaccharides from Aconiturn brachypodum Diels Ameliorate Liver Metastasis via Regulating Treg Cells

目的研究雪上一枝蒿多糖组分XP-10在原发性肝癌肺转移的抑制效应及其作用机理,为雪上一枝蒿多糖肿瘤免疫疗法及南药植物资源合理开发提供科学依据。方法构建H22肝癌肺转移小鼠动物模型,随机分为病理模型组、XP-10低剂量给药组(250 mg/kg)和XP-10高剂量给药组(500 mg/kg),药物干预后,计数肝癌肺内转移灶数目;MTT法检测荷瘤小鼠脾淋巴细胞的活力;流式细胞术检测脾淋巴细胞Th1(CD4^(+)IFN-γ^(+))、Th17(CD4^(+)IL-17A^(+))和Treg细胞(CD4^(+)Foxp3^(+))表达水平。结果XP-10药物干预显著抑制肺转移灶数目(P<0.01),提高荷瘤小鼠淋巴细胞的活力(P<0.01);XP-10低剂量(250 mg/kg)药物干预显著下调荷瘤小鼠CD4^(+)Foxp3^(+)调节性T细胞比例(P<0.05),XP-10药物干预对肝癌肺转移荷瘤小鼠淋巴细胞Th17细胞比例和Th1细胞无显著影响(P>0.05)。结论雪上一枝蒿多糖组分XP-10能够显著抑制原发性肝癌的肺转移,其抑制效应部分通过下调与机体免疫反应负性调节机制相关的Treg细胞,并促进T淋巴细胞增殖、增强抗肿瘤免疫的机制而实现。为中药雪上一枝蒿的多糖抗肿瘤免疫临床疗法提供了一定的现代科学依据。

Objective To study the inhibitory effect and mechanism of polysaccharide XP-10 from Aconiturn brachypodum Diels on lung metastasis of primary liver cancer,and to provide scientific basis for anti-tumor immunotherapy of Aconiturn brachypodum Diels polysaccharide and rational development of southern medicine plant resources.Methods A mouse model of H22 liver cancer with pulmonary metastasis was established and randomly divided into pathological model group,XP-10 low-dose group(250 mg/kg)and XP-10 high-dose group(500 mg/kg).After drug intervention,the number of intrapulmonary metastasis of liver cancer was counted;The viability of splenic lymphocytes in tumor bearing mice was detected by MTT assay.The expression levels of Th1(CD4^(+)IFN-γ^(+)),Th17(CD4^(+)IL-17A^(+))and Treg cells(CD4^(+)Foxp3^(+))in spleen lymphocytes were detected by flow cytometry.Results XP-10 intervention significantly inhibited the number of pulmonary metastatic foci(P<0.01),and increased the proliferation of lymphocytes in tumor bearing mice(P<0.01);XP-10 low dose(250 mg/kg)intervention significantly decreased the proportion of CD4^(+)Foxp3^(+)regulatory T cells in tumor bearing mice(P<0.05),while XP-10 intervention had no significant effect on the proportion of Th17 cells and Th1 cells in lymphocytes of tumor bearing mice with lung metastasis from liver cancer(P>0.05).Conclusion The polysaccharide component XP-10 of Aconiturn brachypodum Diels can significantly inhibit the lung metastasis of primary liver cancer,and its inhibitory effect is partly achieved by downregulating Treg cells related to the negative regulation mechanism of immune response,promoting the proliferation of T lymphocytes,and enhancing the anti-tumor immune mechanism.This provides a certain modern scientific basis for the polysaccharide anti-tumor immunotherapy of traditional Chinese medicine Aconiturn brachypodum Diels in clinical practice.