中国中药杂志

2019, v.44(23) 5184-5190

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基于“补气固表”探究黄芪黄酮组分抑制C57BL/6荷瘤小鼠肿瘤生长及免疫调节机制研究
Mechanism of flavonoid components in Astragali Radix in inhibiting tumor growth and immunoregulation in C57BL/6 tumor bearing mice based on "invigorating Qi for consolidation of exterior"

杨冰;于桂红;李明雨;顾慧敏;陈雅萍;封亮;贾晓斌;
YANG Bing;YU Gui-hong;LI Ming-yu;GU Hui-min;CHEN Ya-ping;FENG Liang;JIA Xiao-bin;School of Traditional Chinese Pharmacy,China Pharmaceutical University;Third Clinical Medical College,Nanjing University of Chinese Medicine;

摘要(Abstract):

传统中医药认为肿瘤的发生发展与机体气虚相关,"补气固表"成为中医药治疗肿瘤的有效途径;该研究基于"补气固表"探究传统补气药黄芪中黄酮组分对小鼠Lewis肺癌移植瘤生长和免疫功能的影响,并进一步探讨其作用机制。采用高效液相色谱法分析并表征黄芪黄酮组分;构建C57BL/6小鼠Lewis肺癌模型,采用Visual Sonics Vevo 2100小动物专用高频彩超评估黄芪黄酮组分对肿瘤体积的抑制作用;分别采用ELISA及免疫组织化学法检测血清及肿瘤组织中IL~(-1)7,RORγt的水平;通过Western bolt法检测肿瘤组织IRE~(-1)/XBP~(-1)通路相关蛋白的表达。结果显示,黄芪黄酮组分低剂量组(5 g·kg~(-1)·d~(-1))和高剂量组(10 g·kg~(-1)·d~(-1))对肿瘤生长均有明显的抑制作用,抑制率分别为(29. 5±4. 4)%,(43. 4±5. 2)%;黄芪黄酮组分能降低C57BL/6荷瘤小鼠血清及肿瘤组织中IL~(-1)7和RORγt表达,并能提高荷瘤小鼠的脾指数及胸腺指数;黄芪黄酮组分能降低X盒结合蛋白1(XBP1)、肌醇酶1(IRE1)及葡萄糖调节蛋白78(GRP78)的表达,升高C/EBP家族同源蛋白(CHOP)的表达,且以高剂量组效果较佳,提示黄芪黄酮组分抗肺癌作用与调控XBP1介导的ERs相关。该研究可为黄芪黄酮组分通过补气固表调节机体免疫功能抑制C57BL/6荷瘤小鼠肿瘤生长提供新的证据。
Traditional Chinese medicine believes that the occurrence and development of tumors is related to the body's Qi deficiency. " Invigorating Qi for consolidation of exterior" has became an effective way to treat tumors by traditional Chinese medicine. This study is based on the " invigorating Qi for consolidation of exterior" to explore the effect of flavonoid components in Qi-invigorating herbs Astragali Radix( AR) on the growth and immune function of mouse Lewis lung cancer xenografts,and further explore its mechanism of action. In the present study,high performance liquid chromatography was performed to analyze the flavonoid components in AR.The Lewis lung cancer model of C57 BL/6 mice was constructed,and the tumor volume of mice was determined by Visual Sonics Vevo2100 high frequency color ultrasound. The levels of IL~(-1)7 and RORγt in serum and tumor tissues were detected by ELISA and immunohistochemistry. The expression of IRE~(-1)/XBP~(-1) pathway-related proteins in tumor tissues was detected by Western blot. The results revealed that treatment of 5 and 10 g·kg~(-1)·d~(-1) of flavonoid components in AR significantly inhibited tumor growth of C57 BL/6 tumorbearing mice. The inhibition rates at the dose of 5 and 10 g·kg~(-1)·d~(-1) of flavonoid components in AR were( 29. 5±4. 4) % and( 43. 4±5. 2) %,respectively. The expression of IL~(-1)7 and RORγt in serum and tumor tissues of Lewis lung cancer mice were decreased,and the spleen index and thymus index were significantly enhanced by the flavonoid components in AR. Flavonoid components in AR could decrease the expression of X-box binding protein 1( XBP1),inositol-requiring enzyme( IRE1) and glucose regulated protein 78 k D( GRP78),and increase the expression of C/EBP homologous protein( CHOP),and the high-dose group is better,suggesting that the anti-lung cancer effect of flavonoid components in AR is related to the regulation of XBP1 mediated ERs. This study provides new evidence that the flavonoid components in AR could inhibit the tumor growth of C57 BL/6 tumor-bearing mice by regulating the body's immune function through " invigorating Qi for consolidation of exterior".

关键词(KeyWords): 黄芪;黄酮组分;补气固表;肺癌;免疫调节;内质网应激
Astragali Radix;flavonoid components;invigorating Qi for consolidation of exterior;lung cancer;immunoregulation;endoplasmic stress

Abstract:

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基金项目(Foundation): 国家中医临床基地建设科研项目(JDZX2015072);; 江苏省六大人才高峰创新团队项目(SWYY-CXTD-004);; 江苏省省科教强卫工程创新团队项目(CXTDB2017003);; 中国药科大学双一流建设创新团队项目(CPU2018GY11,CPU2018GF07);; 国家重点研发计划项目(2018YFC1706900);; 江苏省博士后基金项目(1601023C);; 中国博士后基金项目(2016M601864)

作者(Author): 杨冰;于桂红;李明雨;顾慧敏;陈雅萍;封亮;贾晓斌;
YANG Bing;YU Gui-hong;LI Ming-yu;GU Hui-min;CHEN Ya-ping;FENG Liang;JIA Xiao-bin;School of Traditional Chinese Pharmacy,China Pharmaceutical University;Third Clinical Medical College,Nanjing University of Chinese Medicine;

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