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降钙素基因相关肽转基因预防小鼠自身免疫性糖尿病发病及其抗氧化应激机制

佘飞, 孙威, 毛节明, 王宪

北京大学第三医院血管医学研究所.北京 100083

摘要

CGRP裸质粒直接注射入小鼠双后肢胫前肌,继以程控电针刺激导入(体内电穿孔法),可使血浆和骨骼肌组织CGRP表达水平显著增高,且持续4周以上;注射STZ同时给予CGRP转基因治疗可减轻胰岛#beta#细胞损伤,显著降低自身免疫性糖尿病的发病率及血糖水平;CGRP转基因可显著抑制自身免疫性糖尿病小鼠胰腺局部活性氧和丙二醛的生成,增加过氧化氢酶(CAT)及超氧化物歧化酶(SOD)的活性。结果提示,CGRP裸质粒直接注射、电针辅助导入转基因可获得CGRP持续高水平的表达,能够预防小鼠自身免疫性糖尿病的发病,其机制之一可能为CGRP抑制了活性氧对胰岛#beta#细胞的损伤。

关键词： 自身免疫性糖尿病; 降钙素基因相关肽; 基因治疗; 活性氧

Calcitonin gene-related peptide gene therapy suppresses reactive oxygen species in the pancreas and prevents mice from autoimmune diabetes

She Fei, Sun Wei, Mao Jieming, Wang Xian

Institute of Vascular Medicine,Third Hospital,Peking University.Beijing 100083

Abstract

The CGRP gene therapy decreased morbidity of autoimmune diabetes, and significantly ameliorated hyperglycemia in these mice. CGRP gene transfer inhibited the production of ROS and malondialdehyde (MDA). In addition, it enhanced the activity of catalase (CAT) and superoxide dismutase (SOD) significantly. The data suggest that intramuscular CGRP gene transfer ameliorates autoimmune destruction of islet #beta# cells, resulting in significant reduction in diabetes incidence of MLDS diabetes mice. CGRP benefits might be mediated at least in part by inhibiting the oxidative stress in islet #beta# cells of these mice.

Key words: Insulin-dependent diabetes mellitus;Calcitonin gene-related peptide;Gene therapy;Reactive oxygen species

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引用本文：

佘飞, 孙威, 毛节明, 王宪. 降钙素基因相关肽转基因预防小鼠自身免疫性糖尿病发病及其抗氧化应激机制[J]. 生理学报 2003; 55 (6): .

She Fei, Sun Wei, Mao Jieming, Wang Xian. Calcitonin gene-related peptide gene therapy suppresses reactive oxygen species in the pancreas and prevents mice from autoimmune diabetes. Acta Physiol Sin 2003; 55 (6): (in Chinese with English abstract).