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目的观察转基因方法诱导IL-10过表达对NOD小鼠胰岛形态和功能的保护及其机能。方法 8周龄NOD小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NC组。检测各组胰腺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小鼠血清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小鼠胰腺细胞,减少糖尿病累积发病率,增加胰岛素水平、减轻胰岛炎。TNF-α、IFN-γ水平在Ad-IL-10组低于NC组及Ad-GFP组(P<0.01);Ad-IL-10组胰岛β细胞凋亡率低于Ad-GFP组及NC组(14.1%vs 32.8%vs 35.4%,P<0.01);Fas、Caspase-3蛋白在Ad-IL-10组表达较其他两组降低(P<0.01)。结论 IL-10在NOD小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。
Objective To observe the protection and function of transgenic mice induced by IL-10 overexpression on islet morphology and function in NOD mice. Methods 8-week-old NOD mice were randomly divided into adenovirus-mediated Ad-IL-10 group, adenovirus empty vector Ad-GFP group and NC group. The levels of IL-10, TNF-α and IFN-γ in the serum of NOD mice were measured and the levels of Fas, Caspase-3 expression. Results Intraperitoneal injection of Ad-IL-10 successfully transfected NOD mouse pancreatic cells, reducing the cumulative incidence of diabetes, increasing insulin levels, and reducing insulitis. The levels of TNF-α and IFN-γ in Ad-IL-10 group were lower than those in NC group and Ad-GFP group (P <0.01) (14.1% vs 32.8% vs 35.4%, P <0.01). The expressions of Fas and Caspase-3 protein in Ad-IL-10 group were lower than those in other two groups (P <0.01). Conclusion Overexpression of IL-10 in the pancreas of NOD mice can reduce insulitis, reduce the incidence of diabetes and reduce apoptosis through the Fas pathway.