荷瘤小鼠肝脏中髓源抑制性细胞的生物学特性研究
发布时间：2018-08-02 18:02
【摘要】：髓源抑制性细胞（myeloid-derived suppressor cells，MDSCs）是一群具有强大免疫调控功能的髓系细胞群，主要包括未成熟的树突状细胞、巨噬细胞和粒细胞等。在正常情况下，造血干细胞分化为未成熟髓系细胞（IMCs），IMCs可进一步分化为成熟的树突状细胞、巨噬细胞和（或）粒细胞。而在急慢性炎症、肿瘤、自身免疫性疾病等病理条件下，IMCs的分化受到抑制从而导致MDSCs大量聚集，进而执行免疫抑制功能。MDSCs可聚集在荷瘤动物的骨髓、脾脏、肿瘤组织、外周血中，也可聚集在患者的外周血和肿瘤组织中。最近研究发现，在肝脏原位癌及转移癌模型小鼠的肝脏中有MDSCs的大量增加。而在某些皮下肿瘤模型中，尽管肿瘤并未发生肝脏转移，肝脏中的MDSCs仍然呈增多趋势，这提示肝脏也是MDSCs扩增及归巢的器官。 为了进一步明确肝脏中MDSCs的特点，本实验建立了小鼠皮下肿瘤模型，留取组织标本及血清，利用流式细胞术检测MDSCs在不同组织中的数量变化；光学显微镜、电子显微镜观察其形态；免疫组织化学观察其分布特点；CCK8法检测肝脏MDSCs对T淋巴细胞增殖的影响；ELISA法检测肝脏MDSCs培养上清液中TGF-β1和IL-10表达水平以及不同时间点血清中TGF-β1和IL-6的表达水平，初步探讨肝脏中MDSCs的生物学特性及聚集原因，，旨在为肝脏MDSCs在肝脏微环境中的作用机制研究奠定基础，为今后肝脏疾病治疗提供新的思路。
[Abstract]:Myeloid-derived suppressor cells are a group of myeloid cells with powerful immunomodulatory function, including immature dendritic cells, macrophages and granulocytes. Under normal conditions, hematopoietic stem cells differentiated into immature myeloid cells (IMCs), which further differentiated into mature dendritic cells, macrophages and / or granulocytes. In acute and chronic inflammation, tumor, autoimmune disease and other pathological conditions, the differentiation of MDSCs is inhibited, which leads to a large number of MDSCs aggregation, and then the immunosuppressive function. MDSCs can be clustered in the bone marrow, spleen, tumor tissue of the tumor-bearing animal. Peripheral blood can also be clustered in patients' peripheral blood and tumor tissue. Recent studies have found a significant increase in MDSCs in the liver of mice with liver cancer in situ and metastatic carcinomas. However, in some subcutaneous tumor models, although the tumor did not metastasize, the MDSCs in the liver still tended to increase, suggesting that the liver is also an organ for MDSCs amplification and homing. In order to further understand the characteristics of MDSCs in the liver, a mouse model of subcutaneous tumor was established. Tissue samples and serum were collected. Flow cytometry was used to detect the quantity of MDSCs in different tissues. The morphology was observed by electron microscope and the distribution was observed by immunohistochemistry. The effect of MDSCs on the proliferation of T lymphocytes was detected by CCK8 method. The expression of TGF- 尾 1 and IL-10 in the supernatant of liver MDSCs culture and the expression of TGF- 尾 1 and IL-6 in serum at different time points were detected by ELISA method. The aim of this study is to lay a foundation for the study of the mechanism of liver MDSCs in liver microenvironment and to provide new ideas for the treatment of liver diseases in the future.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R575
本文编号：2160235
[Abstract]:Myeloid-derived suppressor cells are a group of myeloid cells with powerful immunomodulatory function, including immature dendritic cells, macrophages and granulocytes. Under normal conditions, hematopoietic stem cells differentiated into immature myeloid cells (IMCs), which further differentiated into mature dendritic cells, macrophages and / or granulocytes. In acute and chronic inflammation, tumor, autoimmune disease and other pathological conditions, the differentiation of MDSCs is inhibited, which leads to a large number of MDSCs aggregation, and then the immunosuppressive function. MDSCs can be clustered in the bone marrow, spleen, tumor tissue of the tumor-bearing animal. Peripheral blood can also be clustered in patients' peripheral blood and tumor tissue. Recent studies have found a significant increase in MDSCs in the liver of mice with liver cancer in situ and metastatic carcinomas. However, in some subcutaneous tumor models, although the tumor did not metastasize, the MDSCs in the liver still tended to increase, suggesting that the liver is also an organ for MDSCs amplification and homing. In order to further understand the characteristics of MDSCs in the liver, a mouse model of subcutaneous tumor was established. Tissue samples and serum were collected. Flow cytometry was used to detect the quantity of MDSCs in different tissues. The morphology was observed by electron microscope and the distribution was observed by immunohistochemistry. The effect of MDSCs on the proliferation of T lymphocytes was detected by CCK8 method. The expression of TGF- 尾 1 and IL-10 in the supernatant of liver MDSCs culture and the expression of TGF- 尾 1 and IL-6 in serum at different time points were detected by ELISA method. The aim of this study is to lay a foundation for the study of the mechanism of liver MDSCs in liver microenvironment and to provide new ideas for the treatment of liver diseases in the future.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R575
【参考文献】
相关博士学位论文 前1条
1 纪柏;髓样抑制细胞在小鼠肝纤维化发生中的影响机制研究[D];吉林大学;2013年
本文编号：2160235
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