cGVHD诱导小鼠肾炎模型的建立及鉴定

发布时间：2017-12-27 13:16

本文关键词：cGVHD诱导小鼠肾炎模型的建立及鉴定　出处：《天津大学》2010年硕士论文　论文类型：学位论文

【摘要】：移植物抗宿主病(graft-versus-host disease, GVHD)是由移植物中的淋巴细胞识别宿主抗原而活化、增值和分化,直接或间接攻击受者靶组织而发生的一种排斥反应导致的疾病。GVHD主要分为急性移植物抗宿主病(acute GVHD)和慢性移植物抗宿主病(chronic GVHD)两种。二者在发病时间,临床表现呵病理特征上存在很大差别。近年来随着配型技术的不断发展以及新型免疫抑制剂的临床应用,早期急性排斥的发生率明显下降,移植器官的近期存活率得到了显著提高。但是,慢性排斥仍未得到有效预防和控制,最终引起移植器官的功能减退并最终导致移植失败,成为危害患者健康最主要的障碍。因此,寻找更加有效和特异的针对cGVHD的药物成为当务之急。本课题通过建立类似于人类移植物抗宿主病的动物模型,并对该模型进行鉴定,确保模型建立的成功。在此基础上用Rapamycin这一临床药物作为阳性药进行治疗,进一步确定模型构建的成功。从而为筛选更加有效和特异性治疗cGVHD的药物建立了平台,为最终治愈该病做好准备,也为深入了解cGVHD发生发展的规律创造了条件。主要研究结果: (一)以DBA/2J(雌性)小鼠作为供体,B6D2F1小鼠作为受体,取出供体鼠的脾脏,胸腺,以及淋巴结分离出细胞,按细胞数6:3:1的比例,总数达5×10~7进行注射,建立慢性移植物抗宿主病模型。 (二)从小鼠的存活率,尿蛋白发生情况,体重的变化情况以及外周血中抗受着抗体水平的变化,病理组织的观察来确定模型建立的成功。以Rapamycin这一临床用药作为对照,对该模型进行评价。结果表明该模型构建的成功。 (三)建立了筛选针对cGVHD更有效和特异的药物平台,为最终治愈该病并深入了解其发病机理准备了条件。
[Abstract]:Graft-versus-host disease (GVHD) is a kind of rejection disease caused by the activation, increment and differentiation of lymphocytes in the graft, which directly or indirectly attack the recipient's target tissue. GVHD is mainly divided into two types: acute graft versus host disease (acute GVHD) and chronic graft versus host disease (chronic GVHD). There is a great difference between the two in the time of the disease and the pathological features of the clinical manifestation. In recent years, with the continuous development of matching technology and the clinical application of new immunosuppressants, the incidence of early acute rejection has decreased significantly, and the short-term survival rate of transplanted organs has been significantly improved. However, chronic rejection has not been effectively prevented and controlled, which eventually leads to dysfunction of transplanted organs and eventually leads to failure of transplantation, which is the main obstacle to patients' health. Therefore, it is urgent to find more effective and specific drugs for cGVHD.
【学位授予单位】：天津大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R-332;R392

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