本文選題：UBC13　切入點：B6.MRL-Faslpr模型鼠　出處：《山西農(nóng)業(yè)大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：運用自行研制的UBC13蛋白對正常C57鼠及SLE模型鼠進(jìn)行干預(yù),從免疫學(xué)、血清學(xué)、臟器組織形態(tài)學(xué)等方面的指標(biāo)來探討該蛋白對正常C57鼠及SLE模型鼠的免疫干預(yù)效應(yīng)及可能的分子機制。方法：將雌性C57鼠及F2代SLE模型鼠分別隨機分成空白組、PBS組、UBC13組；UBC13蛋白按25mg/kg的劑量腹腔注射于各UBC13組,PBS組注射等量PBS緩沖液,空白組不做任何處理,每日一次,連續(xù)注射10天。第0、5、10天分別眼底靜脈叢采血,取血清用ELISA法檢測外周血中IL-10、IL-17、抗dsDNA抗體、抗核抗體表達(dá)量的變化；第10天處死小鼠,取新鮮脾臟通過流式細(xì)胞術(shù)來檢測脾臟中Treg細(xì)胞的含量變化;測臟器濕重檢測各臟器指數(shù)變化;固定肝臟和腎臟做HE染色病理切片觀察組織病變情況。結(jié)果：在正常C57鼠及SLE模型鼠體內(nèi)試驗中,與空白組和PBS組相比,UBC13組蛋白藥的注射均引起小鼠脾臟腫大,脾臟指數(shù)、腎臟指數(shù)和肝臟指數(shù)顯著升高(P0.05),外周血中抗dsDNA抗體水平和IL-17水平顯著升高(P0.05),脾臟內(nèi)Treg細(xì)胞含量顯著升高(P0.05);但對外周血中IL-10和ANA含量影響不顯著(P0.05)；模型組小鼠腎小球系膜細(xì)胞增多程度不均一,說明此模型腎臟病變程度不一致,個體間差異大；UBC13給藥后均見脾臟腫大,腎臟被膜大量炎細(xì)胞浸潤,可見嗜酸性粒細(xì)胞,肝細(xì)胞炎癥細(xì)胞浸潤且程度不一、纖維蛋白沉積、髓外造血,且見嗜酸性粒細(xì)胞。結(jié)論：UBC13蛋白導(dǎo)致C57鼠及SLE模型鼠外周血中IL-17和抗dsDNA抗體水平顯著提高,但可使脾臟中Treg細(xì)胞含量升高。UBC13用藥劑量及其在機體內(nèi)的作用機制還需進(jìn)一步探討,本研究有望為新的治療自身免疫疾病的藥物研發(fā)方面提供靶標(biāo)。
[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.
【學(xué)位授予單位】：山西農(nóng)業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：S856.9

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本文編號：1582019