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构建含小鼠RegⅢ和胰岛素原基因的双基因质粒,观察其对1型糖尿病小鼠的治疗作用,并初步探讨其作用机制。采用连续小剂量STZ腹腔注射的方法建立1型糖尿病小鼠模型,肌内注射给予RegⅢ/胰岛素原双基因质粒,治疗4周,每周给药1次,动态监测小鼠血糖的变化;并通过Western blotting、ELISA、MTT、HE病理组织学分析及Tunel检测等方法研究其作用机制。结果表明,双基因质粒可显著改善1型糖尿病小鼠的高血糖症状(P<0.01),抑制脾淋巴细胞增殖,恢复1型糖尿病小鼠体内Th1/Th2反应的平衡和胰岛素的正常分泌;HE及Tunel分析表明,双基因质粒可减少胰岛炎性细胞浸润和胰岛细胞的凋亡。提示RegⅢ/胰岛素原双基因质粒对1型糖尿病具有明显的治疗作用,其作用机制与诱导免疫耐受和促进β细胞再生有关。
Construction of double gene plasmids containing mouse Reg Ⅲ and proinsulin gene and their therapeutic effects on type 1 diabetic mice were observed and the mechanism of action was also discussed. The mice model of type 1 diabetes mellitus was established by intraperitoneal injection of continuous small dose of STZ. Reg Ⅲ / proinsulin double gene plasmids were injected intramuscularly for 4 weeks and once a week. The changes of blood glucose in mice were dynamically monitored. Western blotting, ELISA, MTT, HE histological analysis and Tunel test and other methods to study its mechanism. The results showed that the double gene plasmid can significantly improve the symptoms of type 1 diabetic mice hyperglycemia (P <0.01), inhibit the proliferation of splenic lymphocytes and restore the balance of Th1 / Th2 responses and the normal secretion of insulin in type 1 diabetic mice. HE And Tunel analysis showed that the double gene plasmid can reduce islet inflammatory cell infiltration and pancreatic islet cell apoptosis. It is suggested that the RegⅢ / proinsulin double gene plasmid has a significant therapeutic effect on type 1 diabetes mellitus, and its mechanism is related to the induction of immune tolerance and promotion of β cell regeneration.