Objective To explore the protective effect of adenovirus vector mediated murine interleukin 10(Ad-rlL-10) gene on islet beta cells at the early stage of type 1 diabetes in NOD mice. Methods Forty-six NOD mice were randomly divided into four groups: saline control group (ten mice) , diabetes control group (twelve mice) , mock-vehicle control group( twelve mice) and Ad-rIL-10 group( twelve mice). Except the saline control group, the rest mouse were received in-traperitoneal injection of cyclophosphamide in order to induce type 1 diabetes mellitus. After that, Ad-rIL-10 group were immediately received intraperitoneal injection of ad-rIL-10 gene at the dose of 0. 1 mL, mock-vehicle control group were immediately received intraperitoneal injection of ad-eGFP at the dose of 0. 1 mL, and the rest were given equal saline. Body weight and blood glucose of all mice were detected weekly. Three weeks later,all mice were executed, and the serum IL-10, IL-4, INF-7 and C-peptide were detected by enzyme linked immunosorbent assay. Their pancreas were sectioned to observe the degree of insulitis and the local expression of IL-10 gene detected by immunohistochemistry. Results Compared with the saline control group, average blood glucose level and body weight of the other group had significant difference (all P<0.05) , and serum IFN-7 level increased markedly (all P<0.05) , while IL-4, IL-10 and C-peptide level decreased significantly (P <0.05) ; IL-10 gene had a higher expression in Ad-rIL-10 group than that in the other groups (all P < 0.05) ; Among diabetes control group, mock-vehicle control group, Ad-rIL-10 group, the change of blood glucose level, body weight, islet inflammatory infiltration and the serum index were not obvious. Conclusions The administration of Ad-rIL-10 gene dosen't significantly reduce the degree of insulitis, and the early protection on islet p cells of type 1 diabetes mellitus in NOD mice is not obvious.%目的 探讨腺病毒介导的鼠IL-10(Ad-rIL-10)基因对非肥胖型糖尿病(NOD)小鼠1型糖尿病早期胰岛β细胞的保护作用.方法 随机将46只NOD小鼠分为4组:生理盐水对照组10只、糖尿病对照组12只、空载体对照组12只、Ad-rIL-10组12只.除生理盐水对照组外,其他组腹腔注射环磷酰胺诱导糖尿病早期模型.成模后,Ad-rIL-10组立即给予腹腔注射含Ad-rIL-10的重组腺病毒液0.1 mL、空载体对照组给予含Ad-eGFP的重组腺病毒液0.1 mL,其他组给予等量生理盐水.每周检测小鼠体质量、血糖.3周后处死小鼠,留取小鼠血清标本,采用ELISA法测定血清C肽、IFN-γ、IL-4及IL-10水平；制作胰腺标本,免疫组化法观察小鼠胰腺炎症浸润程度和rIL-10局部表达情况.结果 与生理盐水对照组相比,成模后其他组血糖水平、体质量变化有明显差异(P均＜0.05),血清IFN-γ水平明显增高(P均＜0.05),而IL-4、IL-10和C肽水平明显降低(P均＜0.05).糖尿病对照组、Ad-rIL-10组、空载体对照组血糖水平、体质量、胰岛炎症浸润程度及血清学指标变化不明显.结论 Ad-rIL-10基因对NOD小鼠1型糖尿病早期胰岛炎症无明显减轻作用,对残余胰岛β细胞无明显保护作用.
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