B类I型清道夫受体的缺失致小鼠自身免疫疾病相关性淋巴瘤生成的机制研究

项目名称： B类I型清道夫受体的缺失致小鼠自身免疫疾病相关性淋巴瘤生成的机制研究

项目编号： No.81201865

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 淋巴瘤及其他淋巴增殖性疾病

项目作者： 冯虹

作者单位： 山东大学

项目金额： 23万元

中文摘要： 大量临床资料汇总发现系统性自身免疫性疾病患者淋巴瘤发病风险增高。因此研究两者的相关性并寻找这类患者淋巴瘤的高危因素具有重要意义。我们的前期工作发现"老龄SR-BI基因敲除小鼠具有自身免疫性疾病的表现；且易出现异常增大的淋巴结；其中以B细胞来源的增生细胞为主，尤其是B220low亚群；其淋巴滤泡丧失"满天星"的现象"。因此我们提出假说：SR-BI缺失导致自身免疫相关性淋巴瘤的发病风险增加。我们拟"通过体内、外实验进一步确定SR-BI-/-小鼠淋巴瘤细胞的克隆源性及恶性表型；进而用CFSE、细胞周期、Western Blot等证明SR-BI对细胞增殖凋亡、细胞周期和信号通路的影响机制；并改变血清HDL水平观察SR-BI通过胞外环境对淋巴细胞的影响"。从而确立SR-BI的缺失是自身免疫疾病和淋巴瘤高发的共同危险因素，为自身免疫性疾病患者的淋巴瘤的防治提供新的线索和理论依据。

中文关键词： B类I型清道夫受体；乳腺癌；预后；免疫组织化学染色；

英文摘要： Links between systemic autoimmune diseases and increased incidence of lymphoma have been indicated based on series of clinical studies. So it is of great importance to study the association and find out the risk factors. Our previous researches demonstrated that the aged SR-BI-/- mice develop autoimmunity and large lymph nodes. The enlarged nodes are the results of increased B cell-derived lymphocytes, especially the B220low group, while the HE staining of lymph nodes shows the absence of "stars" in lymphoid nodules. Moreover, the B lymphocytes in SR-BI-/- mice have been indicated to be over-activated and hyper-proliferated. Thus our hypothesis is that deficiency of SR-BI induces increased incidences of lymphoma, which is associated to autoimmunity. To accomplish this, we plan to demonstrate the clonal expansion and malignancy of B cell employing experiments both in vivo and in vitro, and study the mechanisms both intracellular and extracellular. Using CFSE, cell cycle and Western Blot, we explore the effects of SR-BI on cell proliferation, apoptosis, cell cycle, and signal transduction. Using high fat and probucol feeding, we expose the influences of dysfunctional HDL on lymphoid phenotype. The aim of this subject is to establish the role of SR-BI in the association of autoimmunity and lymphoma. Our studies pro

英文关键词： Scavenger receptor class B type I；breast cancer；prognosis；immunohistochemistry；