中亚苦蒿免疫调节和抗肝癌活性的物质基础及作用机理研究

Liver cancer is one of the malignant tumors with high morbidity and mortality and poor prognosis. It is a serious threat to the health of people in China and the whole world, but there is a lack of effective treatment drugs or methods. The treatment of spleen inflammation and joint pain has a long history. In this paper, the characteristic medicinal plant of Xinjiang, Artemisia absinthium, was used as the experimental material, and the immune-enhancing and anti-hepatoma components were selected. To further study the mechanism of these immunoenhancing components in enhancing the maturation and function of murine macrophages and DC. The effect of Artemisia absinthium on the growth of hepatoma cells and the mechanism of inducing apoptosis of hepatoma cells were evaluated in vitro. The mouse model of liver cancer was established, and the therapeutic effects of immune enhancement component and hepatoma component of Artemisia absinthium were detected either alone or in combination. In order to explore the therapeutic effect and mechanism of anti-hepatoma drugs and immunopotentiators, this study provides a new idea for the development and utilization of characteristic medicinal resources in Xinjiang, and provides a new strategy for the development of new anti-hepatoma drugs.

肝癌是发病率和死亡率高且预后极差的恶性肿瘤之一，严重威胁我国乃至全世界人民的身体健康，但目前缺乏有效的治疗药物或方法。中亚苦蒿在维吾尔医药中用于肝炎，脾脏炎肿，关节疼痛等治疗，具有悠久的历史。本项目以新疆特色药用植物中亚苦蒿作为研究对象，从中筛选免疫增强组分及抗肿瘤组分，进一步研究这些免疫增强组分增强小鼠巨噬细胞、DC成熟及功能的作用机理，体内对正常小鼠免疫系统的影响及安全性评价。中亚苦蒿抗肿瘤组分对肝癌细胞生长的抑制作用和诱导肝癌细胞凋亡的作用机理，建立H22肝癌小鼠模型，检测中亚苦蒿免疫增强组分及抗肿瘤组分单独或联合对肝癌荷瘤小鼠的治疗作用，探讨其作为免疫增强剂和抗肝癌药物对肝癌的治疗效果及作用机理。本项目为新疆特色药用资源的开发利用提供了新的研究思路，为抗肝癌新药的研制提供了新策略。

肝癌是发病率和死亡率高且预后极差的恶性肿瘤之一，严重威胁我国乃至全世界人民的身体健康，但目前缺乏有效的治疗药物或方法。中亚苦蒿在维吾尔医药中用于肝炎，脾脏炎肿，关节疼痛等治疗，具有悠久的历史。本项目以新疆特色药用植物中亚苦蒿作为研究对象，从中筛选免疫增强组分及抗肿瘤组分，进一步研究这些免疫增强组分增强小鼠树突状细胞成熟及功能的作用机理，体内对正常小鼠免疫系统的影响及安全性评价。中亚苦蒿抗肿瘤组分对肝癌细胞生长的抑制作用和诱导肝癌细胞凋亡的作用机理，建立H22肝癌小鼠模型，检测中亚苦蒿抗肿瘤组分对肝癌荷瘤小鼠的治疗作用，探讨其作为抗肝癌药物对肝癌的治疗效果及作用机理。经提取工艺优化及活性成分富集，中亚苦蒿AAEM-30%组分多糖、黄酮、萜类含量分别为24.30%、22.50%和28.19%，体外能够促进小鼠DC成熟，显著增强小鼠DC表面分子CD40、CD86以及炎症细胞因子IL-6、TNF-α的表达，体内可增强小鼠免疫功能。中亚苦蒿提取物AAEE,AAEE-Pe和AAEE-Ea在体外可通过线粒体依赖和内质网应激途径诱导肝癌细胞凋亡，体内可有效抑制H22细胞生长，提高小鼠存活率，且小鼠没有明显毒副作用。进一步对AAEE分离纯化筛选获得单体化合物氢化奎尼丁，研究表明氢化奎尼丁可通过降低线粒体膜电位、激活caspase通路、激活LC3B和Beclin1诱导肝癌细胞在体内外凋亡和自噬。同时，氢化奎尼丁可以体内抑制肝癌细胞生长并且对小鼠体重和脏器无损伤。因此，氢化奎尼丁可以作为一种潜在的肝癌治疗候选药物。本项目为新疆特色药用资源的开发利用提供了新的研究思路，为抗肝癌新药的研制提供了新策略。