中国动脉硬化杂志2013，Vol.21Issue(8)：711-715,5.
艾塞那肽通过下调p22phox、NOX4和TGF-β1减轻1型糖尿病大鼠主动脉的氧化应激损伤
Exenatide Reduces Oxidative Damage on the Aorta of Type 1 Diabetic Rats by Down-regulating the Over-expression of p22phox, NOX4 and TGF-β1
摘要
Abstract
Aim To observe the effect of glucagon-like peptide-1 receptor agonist exenatide on the expression of NADPH oxidase subunits and oxidative stress damage in the aorta of type 1 diabetic rats.Methods Thirty male Sprague-Dawley(SD) rats were randomly divided into normal control group(n =7) and model group(n =23).Type 1 diabetic model was established by intraperitoneal injection of streptozotocin.Nineteen diabetic rats induced successfully were randomly divided into diabetic group (n =10),and diabetic group treated with exenatide (n =9).Rats in diabetic group treated with exenatide were injected subcutaneously with exenatide in dose of 5 μg/kg twice daily.Rats in normal control group and diabetic group were given equivalent volume of normal saline by subcutaneous injection.All rats were sacrificed after exenatide treatment for eight weeks.The mRNA expression of aortal p22phox and NOX4 were detected by real-time fluorescence quantitative PCR.The protein expression of aortal transforming growth factor-beta (TGF-β1) was detected by immunohistochemical staining.Specimen sections were stained with hematoxylin and eosin for histological examination.Results The mRNA expression of aortal p22phox and NOX4 and the protein expression of aortal TGF-β1 were significantly increased in diabetic group than those in normal control group(P ＜ 0.05).The mRNA expression of aortal p22phox and NOX4 and the protein expression of aortal TGF-β1 were decreased in diabetic group treated with exenatide than those in diabetic group (P ＜ 0.05).Compared with rats in normal control group,rats in diabetic group had the obviously thickened intima and tunica elastica,unsmooth intima,endothelial cell protrusion,the irregular shape of endothelial cells,and the smooth muscle cells arranged in disorder in the aorta.The intima was locally thickened and unsmooth,endothelial cells and smooth muscle cells were arranged in order,and the unica elastica was lightly thickened in the aorta in diabetic group treated with exenatide compared with diabetic group.Conclusions Exenatide can down-regulate the mRNA expression of p22phox and NOX4 and the protein expression of TGF-β1 in the aorta of typel diabetic rats,which can relieve the aortal damage by oxidative stress,thus play a protective role on the blood vessel of diabetic rats.关键词
胰高血糖素样肽1/糖尿病大血管病变/NADPH氧化酶/转化生长因子β1Key words
Glucagon-like Peptide-1/ Diabetic Macrovascular Complications/ NADPH Qxidase/ Transforming Growth Factor-beta 1分类
医药卫生引用本文复制引用
吴杰萍,郭志新,齐伟,俞媛贤,杜时晶,刘晋津..艾塞那肽通过下调p22phox、NOX4和TGF-β1减轻1型糖尿病大鼠主动脉的氧化应激损伤[J].中国动脉硬化杂志,2013,21(8):711-715,5.基金项目
山西省回国留学人员科研资助项目(2011-048),山西医科大学科技创新基金资助项目(01201015) （2011-048）
