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有证据表明,活性氧(reactive oxygen species,ROS)参与了胰岛β细胞自身免疫损伤,是自身免疫性糖尿病发病的重要原因之一。一氧化氮(NO)和过氧化氢(H2O2)介导了致炎性细胞因子对胰岛β细胞的损害,引起脂质过氧化反应,进而损伤胰岛细胞。降钙素基因相关肽(calcitonin gene-related peptide,CGRP)在心肌细胞中可抑制ROS生成而具有细胞保护作用。通过CGRP裸质粒肌肉注射体细胞电针强化转基因方法,使骨骼肌持续表达CGRP,观察其对小剂量多次注射链脲佐菌素(streptozotocin,STZ)造成的小鼠自身免疫性糖尿病发病的影响,进一步测定胰腺局部活性氧含量以及抗氧化酶的改变,探讨其抗氧化应激机制。结果发现,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β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(superoxide dismutase,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
There is evidence that reactive oxygen species (ROS) is involved in the autoimmune damage of pancreatic β-cells and is one of the important causes of autoimmune diabetes. Nitric oxide (NO) and hydrogen peroxide (H2O2) mediate the destruction of pancreatic islet cells by pro-inflammatory cytokines, causing lipid peroxidation and thus damaging islet cells. Calcitonin gene-related peptide (CGRP) has a cytoprotective effect in the inhibition of ROS production in cardiomyocytes. CGRP was stimulated by CGRP intramuscularly somatic cell acupuncture to enhance the expression of CGRP in skeletal muscle and its effect on the development of autoimmune diabetes in mice caused by multiple doses of streptozotocin (STZ) , Further determination of the local active oxygen content in the pancreas and changes in antioxidant enzymes to explore its anti-oxidative stress mechanism. The results showed that the naked plasmid of CGRP was directly injected into the anterior tibialis anterior hindlimb of both hind limbs of mice. Following the programmed electroacupuncture (in vivo electroporation), the expression of CGRP in plasma and skeletal muscle significantly increased for more than 4 weeks. Transfection of STZ with CGRP transgene can reduce the injury of pancreatic β-cells, significantly reduce the incidence of autoimmune diabetes and blood glucose levels; CGRP transgene can significantly inhibit the formation of local reactive oxygen species and malondialdehyde in the pancreas of autoimmune diabetic mice, increased Catalase (CAT) and superoxide dismutase (SOD) activity. The results suggest that direct injection of CGRP naked plasmid, the introduction of electroacupuncture assisted gene transfer CGRP sustained high levels of expression, can prevent the onset of autoimmune diabetes in mice, the machine