本文選題：抗CD20單克隆抗體　切入點(diǎn)：白細(xì)胞介素10　出處：《青島大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：背景:研究發(fā)現(xiàn)肝臟細(xì)胞在給予轉(zhuǎn)入PDX1基因后可合成胰島素,抗CD20單克隆抗體可抑制產(chǎn)胰島素的肝臟細(xì)胞發(fā)生自身免疫反應(yīng),但機(jī)制尚不明確。目的:了解腺病毒介導(dǎo)的鼠白細(xì)胞介素10(Adenovirus vector-mediated murine interleukin,Ad-M IL-10)及抗CD20單克隆抗體聯(lián)合干預(yù)未發(fā)病非肥胖型糖尿病小鼠,對(duì)其肝臟細(xì)胞以及肝臟PDX1表達(dá)的影響。方法:3-5周齡雌性未發(fā)病非肥胖型糖尿病小鼠40只,隨機(jī)分為①抗CD20單克隆抗體組,②抗CD20單克隆抗體+白細(xì)胞介素10組,③白細(xì)胞介素10組,④生理鹽水對(duì)照(Normal control,NC)組。分別于第1天、第8天、第15天及第21天尾靜脈給予注射抗CD20單克隆抗體、抗CD20單克隆抗體+白細(xì)胞介素10、白細(xì)胞介素10和生理鹽水。每周監(jiān)測(cè)小鼠血糖,觀察12周后測(cè)定血清中胰島素、白細(xì)胞介素10及CD20水平。行肝臟病理切片HE染色觀察肝臟細(xì)胞病理變化,免疫組化檢測(cè)肝臟中白細(xì)胞介素10、CD20、胰島素、PDX-1蛋白表達(dá)情況。結(jié)果與結(jié)論:血糖動(dòng)態(tài)曲線圖顯示抗CD20單克隆抗體與白細(xì)胞介素10聯(lián)合干預(yù)控制非肥胖型糖尿病小鼠血糖效果較單獨(dú)干預(yù)組明顯,但單獨(dú)干預(yù)組與對(duì)照組此三組間差異無(wú)統(tǒng)計(jì)學(xué)意義,而聯(lián)合干預(yù)組小鼠血糖與生理鹽水對(duì)照組小鼠血糖實(shí)驗(yàn)前后差異有統(tǒng)計(jì)學(xué)意義,說(shuō)明實(shí)驗(yàn)干預(yù)可以有效控制小鼠血糖。聯(lián)合干預(yù)可增加血清胰島素、白細(xì)胞介素10及CD20表達(dá)水平,使胰島素、CD20及白細(xì)胞介素10在肝臟局部表達(dá)增加,同時(shí)促進(jìn)肝臟PDX-1蛋白表達(dá)。但無(wú)論是聯(lián)合干預(yù)還是單獨(dú)干預(yù)均對(duì)肝臟炎癥病變無(wú)明顯影響。
[Abstract]:Background: it has been found that hepatocytes can synthesize insulin after transfection into PDX1 gene, and anti CD20 monoclonal antibody can inhibit the autoimmune reaction of insulin-producing hepatocytes. Objective: to investigate the effects of adenovirus-mediated adenovirus vector-mediated murine interleukin-M IL-10 and anti-#en2# monoclonal antibody on nonobese diabetic mice. Methods 40 female non-obese diabetic mice aged 3 to 5 weeks were selected. They were randomly divided into two groups: 1 anti CD20 monoclonal antibody group, 2 anti CD20 monoclonal antibody group, IL 10 group, 3 IL 10 group, 4 normal control normal control group, respectively on day 1 and day 8, respectively. On the 15th and 21st day, the mice were injected with CD20 monoclonal antibody, anti CD20 monoclonal antibody interleukin 10, interleukin 10 and normal saline. The blood glucose of mice was monitored weekly, and the serum insulin was measured after 12 weeks. The levels of interleukin 10 and CD20. The pathological changes of liver cells were observed by HE staining in liver sections. Immunohistochemistry was used to detect the expression of interleukin-10 CD20, insulin and PDX-1 protein in liver. Results and conclusion: the dynamic curve of blood glucose showed that the combination of anti CD20 monoclonal antibody and interleukin 10 was used to control non-obese diabetic mice. The effect of blood glucose was more obvious than that of the single intervention group. However, there was no significant difference between the three groups, but the blood glucose of mice in the combined intervention group and the saline control group was significantly different before and after the experiment. The results showed that the experimental intervention could effectively control the blood glucose in mice. The combined intervention could increase the expression of serum insulin, interleukin 10 and CD20, and increase the expression of insulin CD20 and interleukin 10 in the liver. At the same time, the expression of PDX-1 protein in liver was promoted, but there was no significant effect on hepatic inflammatory lesion in combination or alone intervention.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R725.8

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