腺病毒介导的IL-10基因对1型糖尿病发病早期NOD鼠胰岛β细胞的保护作用  

Protective effect on pancreas islet β cells of NOD mouse derived from adenovirus vector-mediated murine IL-10 genes in early phase of type 1 diabetes mellitus

作　　者：李诚[1] 林晓杰[1] 陈燕燕[1] 张丽娟[1] 李堂[1] 

机构地区：[1]青岛大学附属医院,山东青岛266003

出　　处：《山东医药》2014年第43期12-15,共4页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81170762);山东省自然科学基金资助项目(Y2008C50)

摘　　要：目的：观察腺病毒介导的IL-10（Ad-mIL-10）基因干预对1型糖尿病（T1DM）发病早期的非肥胖型糖尿病（ NOD）鼠胰岛β细胞的保护作用。方法选取17～20周龄近期发病（诊断为T1DM不超过3 d）的雌性NOD小鼠12只，随机分为A、B组（各6只），A组发病后立即予腹腔注射0．1 mL的Ad-mIL-10，B组未予任何干预；另选取相同周龄未发病的NOD鼠6只为C组，未予任何干预。实验前及实验开始后的第1、2、3周记录小鼠体质量、尿糖及血糖；第3周时处死全部小鼠，摘眼球法取全血并测血清 IL-10、IFN-γ、IL-4和 C肽；取胰腺做病理切片，HE及免疫组化染色，观察小鼠胰岛炎性浸润程度及IL-10基因在胰腺的表达情况。结果与B组相比，A组胰腺局部IL-10高表达、血清IL-10水平升高（P＜0．01）；A组血清IFN-γ水平较B组降低、IL-4及IL-10水平较B组升高、IFN-γ／IL-4较B组降低，两组相比， P均＜0．01；A组血清C肽水平较B组升高，两组相比，P＜0．01。结论 Ad-mIL-10基因干预可对自然发病NOD小鼠发挥一定的免疫调节作用，一定程度上改善其胰岛β细胞功能。Objective To obverse the protective effect on pancreas islet βcells of nonobese diabetic （ NOD） mouse in early phase of type 1 diabetes mellitus caused by adenovirus vector-mediated murine IL-10（ Ad-mIL-10） genes.Methods 12 female NOD mice of 17-20 weeks old with diagnosis of type 1 diabetes mellitus less than 3 days were collected and random-ly divided into group A and B （ 6 mice in each group ） .Mice in group A were intraperitoneal injected with Ad-mIL-10 （0.1 mL） immediately in the early stage of diabetes and those in group B were treated with nothing as control .In addition, 6 NOD mice which in same age range and at inactive stage of disease were selected as group C , without any intervention .Data of weight, urine and blood sugar of mice at 4 time points which before the trial and 1, 2, 3 weeks after beginning were recor-ded for analysis .All mice were condemned to death in the third week , and whole blood was collected by method of picking eyeball, which then was used for measurement of IL-10, IFN-γ, IL-4 and C-peptide in blood serum.Several pathological sec-tions from pancreas which stained with HE and Immunohistochemistry assay were collected to analyze the infiltration degree of pancreas islet and expression of IL-10 genes in pancreas .Results Compared with group B , group A showed high IL-10 ex-pression in local pancreas and increased IL-10 figures in blood serum（P〈0.01）.In group A, the data of measured IFN-γand IFN-γ/IL-4 were lower than those of group B , whereas, IL-4 and IL-10 were detected in higher expression （ all P〈0.01）.C-peptide level in serum was more significant in group A （P〈0.01）.Conclusions IL-10 gene intervention has an immunomodulatory role on spontaneous disease of NOD mice .It can improve the function of islet beta cells to a certain ex-tent, but has no effect on insulitis alleviation and blood glucose control .

关 键 词：糖尿病 1型糖尿病 白细胞介素10 免疫疗法 非肥胖型糖尿病鼠 

分 类 号：R725.8[医药卫生—儿科]