抗CD20单克隆抗体与IL-10基因联合干预未发病非肥胖型糖尿病小鼠对其肝脏PDX1表达的影响

发布时间：2018-03-07 09:21

本文选题：抗CD20单克隆抗体　切入点：白细胞介素10　出处：《青岛大学》2015年硕士论文　论文类型：学位论文

【摘要】：背景:研究发现肝脏细胞在给予转入PDX1基因后可合成胰岛素,抗CD20单克隆抗体可抑制产胰岛素的肝脏细胞发生自身免疫反应,但机制尚不明确。目的:了解腺病毒介导的鼠白细胞介素10(Adenovirus vector-mediated murine interleukin,Ad-M IL-10)及抗CD20单克隆抗体联合干预未发病非肥胖型糖尿病小鼠,对其肝脏细胞以及肝脏PDX1表达的影响。方法:3-5周龄雌性未发病非肥胖型糖尿病小鼠40只,随机分为①抗CD20单克隆抗体组,②抗CD20单克隆抗体+白细胞介素10组,③白细胞介素10组,④生理盐水对照(Normal control,NC)组。分别于第1天、第8天、第15天及第21天尾静脉给予注射抗CD20单克隆抗体、抗CD20单克隆抗体+白细胞介素10、白细胞介素10和生理盐水。每周监测小鼠血糖,观察12周后测定血清中胰岛素、白细胞介素10及CD20水平。行肝脏病理切片HE染色观察肝脏细胞病理变化,免疫组化检测肝脏中白细胞介素10、CD20、胰岛素、PDX-1蛋白表达情况。结果与结论:血糖动态曲线图显示抗CD20单克隆抗体与白细胞介素10联合干预控制非肥胖型糖尿病小鼠血糖效果较单独干预组明显,但单独干预组与对照组此三组间差异无统计学意义,而联合干预组小鼠血糖与生理盐水对照组小鼠血糖实验前后差异有统计学意义,说明实验干预可以有效控制小鼠血糖。联合干预可增加血清胰岛素、白细胞介素10及CD20表达水平,使胰岛素、CD20及白细胞介素10在肝脏局部表达增加,同时促进肝脏PDX-1蛋白表达。但无论是联合干预还是单独干预均对肝脏炎症病变无明显影响。
[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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R725.8

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