多房棘球蚴感染小鼠髓源抑制性细胞促肝脏寄生部位血管生成作用的研究

Echinococcosis is an important life-threatening zoonoses worldwide. And alveolar echinococcosis, also known as worm cancer, is much more serious with higher mortality. Because its pathogen-alveolar hydatid, mainly parasitizes in host’s liver with new cysts continuously resulting in granuloma formation, hyperblastosis and cellular infiltration, which will promote the development of alveolar hydatid. Moreover, angiogenesis develops in the focus of infection resulting in diffuse infiltration and metastasis like malignant tumor growth. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid cells that include immature macrophages, dentritic cells, granulocytes and other myeloid cells at earlier stages of differentiation, plays a role in immunosuppression in the tumor microenvironment, and also significantly promots tumor angiogenesis through some pathways such as secreting angiogenic factors or differentiating into endothelial cells, eventually provides nutrients for tumor infiltration as the basis of tumor growth and metastasis. And MDSCs increase due to the infection of hydatid cyst, but the distribution of MDSCs and their roles in angiogenesis during hepatic alveolar hydatid infection are unclear, it deserves further researches. Therefore, we will study the distribution of MDSCs and their subtypes during hepatic alveolar hydatid infection through several methods such as flow cytometry, and focus on the relationship between liver MDSCs and angiogenesis in the parasitized location through mouse angiogenesis antibody array, transcriptome sequencing, immunohistochemistry and tubule formation assay and so on, using the Balb/c mice suffered from hepatic alveolar hydatid infection, and verify it through the corresponding experiments using anti-MDSCs antibody in the present project. Finally, we will explore the mechanism of MDSCs in promoting angiogenesis in this animal infection model preliminarily. The results will provide scientific basis for the control of alveolar hydatid infiltration and metastasis in hosts, and also provide new ideas for the treatment of echinococcosis.

包虫病是严重危害人民健康的重要人兽共患病，是我国重点防控的重大疾病。泡型包虫病尤为严重，其病原多房棘球蚴感染宿主肝脏后不断产生囊伴肉芽肿反应、细胞浸润和组织增生，寄生部位有血管生成，促进棘球蚴生长，似恶性肿瘤，俗称“虫癌”。髓源抑制性细胞（MDSCs）在肿瘤微环境中通过分泌血管生成因子或分化为内皮细胞等途径促血管生成，是肿瘤浸润、侵袭和转移的关键。宿主感染棘球蚴后MDSCs比例升高，是否对多房棘球蚴感染肝脏寄生部位的血管生成有重要作用未见报道。本研究拟通过流式细胞术等免疫学方法研究多房棘球蚴感染肝脏小鼠MDSCs及其亚型的分布特征，通过血管生成因子抗体芯片、转录组测序、免疫组化法和内皮细胞成管试验等研究MDSCs与寄生肝脏部位血管生成的关系，并应用抗MDSCs抗体反向验证，初步阐明MDSCs对血管生成的作用，为控制多房棘球蚴在体内浸润生长和转移研究提供科学依据，也为包虫病治疗提供新思路。

包虫病是严重危害人民健康的重要人兽共患病，是我国重点防控的重大疾病。泡型包虫病尤为严重，其病原多房棘球蚴感染宿主肝脏后不断产生囊伴肉芽肿反应、细胞浸润和组织增生，寄生部位有血管生成，促进棘球蚴生长，似恶性肿瘤，俗称“虫癌”。髓源抑制性细胞（MDSCs）在肿瘤微环境中通过分泌血管生成因子或分化为内皮细胞等途径促血管生成，是肿瘤浸润、侵袭和转移的关键。本研究通过流式细胞术等免疫学方法研究棘球蚴感染小鼠MDSCs及其亚型的分布特征，通过血管生成因子抗体芯片、转录组测序、免疫组化法和内皮细胞成管试验等研究MDSCs与寄生部位血管生成的关系，发现多房棘球蚴不同感染阶段小鼠MDSCs的组织分布不平衡，多房棘球蚴感染后微环境中血管生成相关分子高表达，MDSCs体外促HUVEC血管生成，以及单核MDSCs的mRNA和非编码RNA潜在调控宿主血管生成，发现了MDSCs中一些具有潜在促血管生成的分子，值得进一步深入研究，为控制棘球蚴在体内浸润生长和转移研究提供科学依据，也为包虫病治疗提供新思路。