UBC13对C57鼠及SLE模型鼠免疫功能的影响

发布时间：2018-03-08 02:26

本文选题：UBC13　切入点：B6.MRL-Faslpr模型鼠　出处：《山西农业大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的：运用自行研制的UBC13蛋白对正常C57鼠及SLE模型鼠进行干预,从免疫学、血清学、脏器组织形态学等方面的指标来探讨该蛋白对正常C57鼠及SLE模型鼠的免疫干预效应及可能的分子机制。方法：将雌性C57鼠及F2代SLE模型鼠分别随机分成空白组、PBS组、UBC13组；UBC13蛋白按25mg/kg的剂量腹腔注射于各UBC13组,PBS组注射等量PBS缓冲液,空白组不做任何处理,每日一次,连续注射10天。第0、5、10天分别眼底静脉丛采血,取血清用ELISA法检测外周血中IL-10、IL-17、抗dsDNA抗体、抗核抗体表达量的变化；第10天处死小鼠,取新鲜脾脏通过流式细胞术来检测脾脏中Treg细胞的含量变化;测脏器湿重检测各脏器指数变化;固定肝脏和肾脏做HE染色病理切片观察组织病变情况。结果：在正常C57鼠及SLE模型鼠体内试验中,与空白组和PBS组相比,UBC13组蛋白药的注射均引起小鼠脾脏肿大,脾脏指数、肾脏指数和肝脏指数显著升高(P0.05),外周血中抗dsDNA抗体水平和IL-17水平显著升高(P0.05),脾脏内Treg细胞含量显著升高(P0.05);但对外周血中IL-10和ANA含量影响不显著(P0.05)；模型组小鼠肾小球系膜细胞增多程度不均一,说明此模型肾脏病变程度不一致,个体间差异大；UBC13给药后均见脾脏肿大,肾脏被膜大量炎细胞浸润,可见嗜酸性粒细胞,肝细胞炎症细胞浸润且程度不一、纤维蛋白沉积、髓外造血,且见嗜酸性粒细胞。结论：UBC13蛋白导致C57鼠及SLE模型鼠外周血中IL-17和抗dsDNA抗体水平显著提高,但可使脾脏中Treg细胞含量升高。UBC13用药剂量及其在机体内的作用机制还需进一步探讨,本研究有望为新的治疗自身免疫疾病的药物研发方面提供靶标。
[Abstract]:Objective: to study the effects of UBC13 protein on normal C57 mice and SLE model rats. To study the immunological intervention effect and possible molecular mechanism of the protein on normal C57 mice and SLE model mice, the female C57 mice and F2 generation SLE model mice were randomly divided into blank group. UBC13 protein was injected intraperitoneally at a dose of 25 mg / kg into each UBC13 group, and the same amount of PBS buffer was injected into the PBS group. In the blank group, blood was collected from the eyeground venous plexus once a day for 10 days. The blood samples were collected from the venous plexus of the eye fundus respectively. The changes of IL-10 IL-17, anti dsDNA antibody and anti nuclear antibody expression in peripheral blood were detected by ELISA method, and the mice were killed on the 10th day. Fresh spleen was collected to detect the content of Treg cells in spleen by flow cytometry, and the index of each organ was measured by measuring the wet weight of organs. Results: in vivo test of normal C57 mice and SLE model mice, the injection of UBC13 protein drugs caused splenomegaly and spleen index in mice compared with blank group and PBS group. The renal index and liver index increased significantly (P 0.05), the level of anti dsDNA antibody and IL-17 in peripheral blood increased significantly (P 0 05), and the content of Treg cells in spleen increased significantly (P 0 05), but the content of IL-10 and ANA in peripheral blood was not affected significantly (P 0 05). The degree of proliferation of Mesangial cells was not uniform. The results showed that the degree of renal lesions in this model was not consistent. After administration of UBC13, there were splenomegaly, a large number of inflammatory cells in renal capsule, eosinophilic granulocytes, inflammatory cells in hepatocytes and fibrin deposition. Conclusion the levels of IL-17 and anti dsDNA antibodies in peripheral blood of C57 mice and SLE model rats were significantly increased by the presence of eosinophil. However, the dose of UBC13 could increase the content of Treg cells in spleen and the mechanism of UBC13 administration in the body should be further explored. This study is expected to provide a target for the development of new drugs for the treatment of autoimmune diseases.
【学位授予单位】：山西农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S856.9

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