【摘要】：髓源抑制性細(xì)胞（myeloid-derived suppressor cells，MDSCs）是一群具有強(qiáng)大免疫調(diào)控功能的髓系細(xì)胞群，主要包括未成熟的樹(shù)突狀細(xì)胞、巨噬細(xì)胞和粒細(xì)胞等。在正常情況下，造血干細(xì)胞分化為未成熟髓系細(xì)胞（IMCs），IMCs可進(jìn)一步分化為成熟的樹(shù)突狀細(xì)胞、巨噬細(xì)胞和（或）粒細(xì)胞。而在急慢性炎癥、腫瘤、自身免疫性疾病等病理?xiàng)l件下，IMCs的分化受到抑制從而導(dǎo)致MDSCs大量聚集，進(jìn)而執(zhí)行免疫抑制功能。MDSCs可聚集在荷瘤動(dòng)物的骨髓、脾臟、腫瘤組織、外周血中，也可聚集在患者的外周血和腫瘤組織中。最近研究發(fā)現(xiàn)，在肝臟原位癌及轉(zhuǎn)移癌模型小鼠的肝臟中有MDSCs的大量增加。而在某些皮下腫瘤模型中，盡管腫瘤并未發(fā)生肝臟轉(zhuǎn)移，肝臟中的MDSCs仍然呈增多趨勢(shì)，這提示肝臟也是MDSCs擴(kuò)增及歸巢的器官。 為了進(jìn)一步明確肝臟中MDSCs的特點(diǎn)，本實(shí)驗(yàn)建立了小鼠皮下腫瘤模型，留取組織標(biāo)本及血清，利用流式細(xì)胞術(shù)檢測(cè)MDSCs在不同組織中的數(shù)量變化；光學(xué)顯微鏡、電子顯微鏡觀察其形態(tài)；免疫組織化學(xué)觀察其分布特點(diǎn)；CCK8法檢測(cè)肝臟MDSCs對(duì)T淋巴細(xì)胞增殖的影響；ELISA法檢測(cè)肝臟MDSCs培養(yǎng)上清液中TGF-β1和IL-10表達(dá)水平以及不同時(shí)間點(diǎn)血清中TGF-β1和IL-6的表達(dá)水平，初步探討肝臟中MDSCs的生物學(xué)特性及聚集原因，，旨在為肝臟MDSCs在肝臟微環(huán)境中的作用機(jī)制研究奠定基礎(chǔ)，為今后肝臟疾病治療提供新的思路。
[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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R575

【參考文獻(xiàn)】

相關(guān)博士學(xué)位論文 前1條

1 紀(jì)柏;髓樣抑制細(xì)胞在小鼠肝纖維化發(fā)生中的影響機(jī)制研究[D];吉林大學(xué);2013年

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