黄芪皂苷II抗肝癌肺转移效应及作用机理的研究  

Effect and Mechanism of Astragaloside II on Pulmonary Metastatic of Hepatoma in Mice

作　　者：王敏[1] 郑喜 祁燕 普晓佳 张霞 李小丝 刘蓓 万春平 Wang Min;Zheng Xi;Qi Yan;Pu Xiaojia;Zhang Xia;Li Xiaosi;Liu Bei;Wan Chunping(Accident and emergency departments,The First People's Hospital of Yunnan Province,Kunming 650021;Central Laboratory,The NO.1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine(TCM),Kunming 650021;College of Pharmaceutical Science,Yunnan University of Traditional Chinese Medicine,Kunming 650500)

机构地区：[1]云南省第一人民医院急诊科,昆明650032 [2]云南中医药大学第一附属医院中心实验室,昆明650021 [3]云南中医药大学中药学院,昆明650021

出　　处：《中药药理与临床》2019年第6期41-45,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(项目编号:81460624、81960745);云南省自然基金面上项目(项目编号:2015FB199);云南省科学技术厅-云南中医学院应用基础研究联合专项(项目编号:2017FF117(-041)).

摘　　要：目的:研究黄芪皂苷对原发性肝癌肺转移抑制效应及作用机理。方法:建立H22肝癌肺转移模型,随机分为荷瘤模型组、黄芪皂苷II 0.3 mg/kg、1 mg/kg组和黄芪皂苷II 0.3 mg/kg+抗CD451000 mg/kg抗体组。药物干预后,检测肺内肿瘤转移数和肺病理损伤程度;酶联免疫吸附(ELISA)法检测Th1细胞因子(IL-2和IFN-γ)产生水平;流式细胞术检测脾淋巴细胞Ki-67和胞内Th1细胞表达水平;Western blot检测脾淋巴细胞LCK(phospho-Tyr505)和STAT1磷酸化水平。结果:与模型组比较,黄芪皂苷0.3 mg/kg、1 mg/kg药物干预组肺转移灶数目显著减少,肺转移病理损伤减轻,荷瘤小鼠淋巴细胞的增殖功能(CD4^+Ki67+T细胞)明显增加,Th1型细胞因子IFN-γ和IL-2的产生明显增加,肝癌肺转移荷瘤小鼠淋巴细胞Th1细胞(CD4^+IFN-γ)比例明显上调,促进LCK(phospho-Tyr505)去磷酸化。抗CD45抗体干预显著阻断黄芪皂苷II抗肺转移效应和促增殖作用,明显减少黄芪皂苷II促Th1型细胞因子(IFN-γ和IL-2)的产生和Th1细胞表达水平。同时抗CD45抗体干预显著阻断黄芪皂苷II促LCK 505位去磷酸化。结论:黄芪皂苷具有显著抗肺转移效应,其作用机理与激活CD45蛋白酪氨酸磷酸酯酶,从而促进Th1细胞因子释放及T淋巴细胞的激活有关。Objective:To study the effect and mechanism of Astragaloside II on pulmonary metastasis and its molecular mechanism.Methods:The experimental murine H22 metastasis model was established.After modeling,mice were divided randomly into the model group,Astragaloside II groups(0.3 mg/kg,1 mg/kg)and 0.3 mg/kg Astragaloside II combined with anti-CD45(1000 mg/kg)group.After administration,the number of tumor metastasis and pulmonary histological changes were observed.Th1 cytokine(IFN-γand IL-2)production levels were assessed by ELISA.CD4^+Ki67+T cell and Th1 intracellular cytokines(IFN-γ)were detected by flow cytometry.The phosphorylation level of LCK(phospho-Tyr505)and STAT1 was assessed by western blot.Results:Compared with the model group,the number of tumor metastasis was reduced in Astragaloside II treatment groups(0.3 mg/kg,1 mg/kg),pathological injury were improved,the lymphocyte proliferation activity(CD4^+Ki67+T)was enhanced,the production of Th1 cytokine(IFN-γand IL-2)was increased,the expression of Th1 cell(CD4^+IFN-γ)was up-regulated,the dephosphorylation of LCK(Tyr-505)was promoted.In Astragaloside II combined with anti-CD45 group,the anti-lung metastasis and lymphocyte proliferation activity were blocked,the levels of Th1 cytokine(IFN-γand IL-2)and Th1 intracellular cytokines(IFN-γexpression were decreased,also the dephosphorylation of LCK(Tyr-505)was blocked.Conclusion:Astragaloside has the inhibitory effect on pulmonary metastasis,its mechanism may be related to activating CD45 protein tyrosine phosphatase,promoting the release of Th1 cell and activating the lymphocyte T cell.

关 键 词：黄芪皂苷 肺转移 CD45蛋白酪氨酸磷酸酯酶 辅助性Th1细胞 抗肿瘤免疫 

分 类 号：R285.5[医药卫生—中药学]