·糖尿病基础研究·

　　【摘要】 目的 观察转基因方法诱导IL-10过表达对NOD鼠胰岛形态和功能的保护及其机能。 方法 8周龄NOD鼠随机分为腺病毒介导IL-10(Ad-IL-10)组、腺病毒空载体Ad-GFP(Ad-GFP)组及Con组。检测各组小鼠胰腺IL-10的表达，外周血胰岛素水平;观察胰腺组织形态变化;检测NOD鼠血清IL-10、TNF-α、IFN-γ水平;测定胰岛细胞凋亡及Fas、Caspase-3的表达。 结果 腹腔注射Ad-IL-10可成功转染NOD鼠胰腺细胞，减少糖尿病累积发病率，增加胰岛素水平、降低胰岛炎。TNF-α、IFN-γ水平在Ad-IL-10组低于Con组及Ad-GFP组(P<0.01);Ad-IL-10组β细胞凋亡率低于Ad-GFP组及Con组(14.1 % vs 32.8 % vs 35.4 %,P<0.01);Fas、Caspase-3蛋白在Ad-IL-10组表达较其他两组减低(P<0.01)。 结论 IL-10在NOD鼠胰腺组织过表达可以减轻胰岛炎，减少糖尿病的发生，通过Fas途径减少细胞凋亡。

　　【关键词】IL-10;基因;凋亡;NOD鼠

Effect of gene transfer-induced IL-10 over-expression on morphology and function of pancreatic beta cells XU Ai-jing, CHEN Zhi-hong, YAN Li-Hua, et al. Guangzhou Women and Children's Medical Center, Guangzhou 510520, China

Corresponding author: LI Tang, E-mail:litang@qd-public.sd.cninfo.net

　　【Abstract】 Objective To explore the effect and mechanism of IL-10 gene transfer on morphology and function of pancreatic beta cells in NOD mice. Methods Female NOD mice, aged 8 weeks, were randomized into 3 groups: control group, Ad-GFP group and Ad-IL-10 group. Before and during the experiment, the blood glucose of all mice was assessed. Pancreata were removed from NOD mice at the 16th week of age in each group and their insulitis severity was scored by routine H-E staining. The levels of IL-10, TNF-α, IFN-γ and insulin in sera were measured by the ELISA method. The apoptosis of pancreatic β-cells was determined by Tunel assay and the expressions of Fas and caspase-3 were estimated by immunohistochemistry analysis. Results There was a significant reduction of diabetes incidence in NOD mice treated with IL-10 gene. The insulitis score of the Ad-IL-10 group was lower than that of the control group and Ad-GFP group (P<0.01). The level of IL-10 in sera was higher and TNF-α and IFN-γ were lower in the Ad-IL-10 group than those in the control group (P<0.01). The apoptosis of β cells was lower in the Ad-IL-10 group than in the Ad-GFP group and the control group (14.1 % vs 32.8 % vs 35.4 %, P<0.01) by Tunel assay. The expressions of Fas and caspase-3 were decreased in the Ad-IL-10 group than in the other two groups (P<0.01). Conclusions The gene transfer-induced IL-10 over-expression alleviates the insulitis of NOD mice, reduces the incidence of diabetes, and reduces the apoptosis via decreasing the expression of Fas.

　　【Key words】Interleukin-10; Gene; Apoptosis; NOD mice