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目的:研究编码白介素-10(IL-10)质粒DNA对由多次、低剂量链脲佐菌素(STZ)诱发的自身免疫性糖尿病小鼠的作用。方法:连续5天将STZ(每次40 mg/kg)腹腔注射入小鼠体内,于第1、14天将100 mg表达人IL-10-pcDNA3质粒(IL-10处理组)或pcDNA3质粒(对照组)注射入骨骼肌内。测定小鼠血糖水平。第28天处死小鼠,检测小鼠血清干扰素-γ(IFN-γ)水平、胰腺IL 1β和TNF-α mRNA表达,测定脾CD4~+和CD8~+淋巴细胞的数量,同时进行胰腺组织学检查。结果:IL-10质粒DNA注射后,骨骼肌有IL-10 mRNA的持久表达,血浆IL-10水平明显升高,而且对迟发性超敏反应具抑制作用。IL-10处理组,在14、21和28天小鼠血糖显著降低,在21、28天时糖尿病发病率分别为33.3％和40.0％,显著低于对照组(P<0.05);胰腺IL-1β和TNF-αmRNA表达、血清IFN-γ水平,以及脾CD4~+和CD8~+淋巴细胞数量均低于对照组,胰岛炎症程度也明显轻于对照组(P<0.01)。结论:IL-10基因治疗能减轻实验性自身免疫性糖尿病小鼠 的胰岛炎症,降低糖尿病发生的机率。
AIM: To investigate the effect of interleukin-10 (IL-10) plasmid DNA on autoimmune diabetes in mice induced by multiple, low doses of streptozotocin (STZ). Methods: STZ (40 mg / kg each time) was injected intraperitoneally into mice for 5 days. 100 mg of IL-10-pcDNA3 plasmid (IL-10 group) or pcDNA3 plasmid Control group) injected into skeletal muscle. Mouse blood glucose levels were measured. The mice were sacrificed on the 28th day, the level of IFN-γ, the expression of IL-1β and TNF-α mRNA in the pancreas were detected, and the numbers of splenic CD4 ~ + and CD8 ~ + lymphocytes were measured. School inspection. Results: After IL-10 plasmid DNA injection, the skeletal muscle had persistent expression of IL-10 mRNA, the level of plasma IL-10 was significantly increased, and it also inhibited the delayed hypersensitivity. In the IL-10 group, the blood glucose of mice was significantly decreased at 14, 21 and 28 days. The incidence of diabetes was 33.3% and 40.0% at 21 and 28 days, respectively, significantly lower than that of the control group (P <0.05) The level of IFN-γ, the number of CD4 ~ + and CD8 ~ + lymphocytes in the spleen were lower than those in the control group, and the degree of insulitis was also significantly lower than that in the control group (P <0.01). Conclusion: IL-10 gene therapy can reduce islet inflammation and reduce the incidence of diabetes in experimental autoimmune diabetic mice.