替米沙坦对db/db小鼠胰岛内NADPH氧化酶表达水平的影响  

Effects of telmisartan on the expression of NADPH oxidase in the pancreatic islet of db/db mice

作　　者：邵加庆[1] 顾萍[1] 杜宏[1] 卢斌[1] 李洁[1] 彭丽[1] 王燕燕[1] 赵明[1] 王坚[1] 

机构地区：[1]南京军区南京总医院内分泌科,南京医学博士210002

出　　处：《医学研究生学报》2010年第7期680-683,共4页Journal of Medical Postgraduates

基　　金：国家自然科学基金(30900697);江苏省自然科学基金(BK2007574);江苏省"六大人才高峰"高层次人才培养对象C类基金

摘　　要：目的大规模流行病学研究显示,血管紧张素ⅡAT1受体拮抗剂(angiotensinⅡAT1receptor antagonist,ARB)能减少2型糖尿病的发生,但其机制尚未阐明。文中拟探讨使用替米沙坦阻断肾素-血管紧张素系统对db/db小鼠胰岛内NADPH氧化酶表达水平的影响。方法将22只8周龄db/db小鼠随机分为2组,替米沙坦组和db/db对照组,每组11只,分别给予替米沙坦5mg/(kg.d)和安慰剂灌胃。另设11只同周龄db/m小鼠也给予安慰剂灌胃作为非糖尿病对照,为db/m对照组。每周监测体重、血糖,6周后行腹腔葡萄糖耐量试验,并取胰腺行免疫组化,分析胰岛内NADPH氧化酶表达情况。结果替米沙坦降低了db/db小鼠血糖,改善胰岛素分泌功能和胰岛素敏感性,显著降低了胰岛内NADPH氧化酶gp91phox、p22phox亚基的表达水平。结论替米沙坦阻断AT1受体可改善胰岛微环境,降低NADPH氧化酶的表达,减少氧化应激的来源,从而保护胰岛β细胞。Objective Epidemiological studies have suggested that the angiotensin Ⅱ type 1 receptor blocker （ARB） may reduce the risk of type 2 diabetes,but its mechanisms remain to be elucidated.The aim of this study was to explore the effects of telmisartan on the intra-islet levels of NADPH oxidase in db/db mice.Methods Twenty-two db/db mice,8 weeks of age,were equally randomized to two groups to receive placebo and telmisartan at 5 mg/kg daily via gavage.Another 11 age-matched db/misty mice were treated with placebo as non-diabetic controls.Body weight and random blood glucose were measured every week.The intraperitoneal glucose tolerance test and immunohistochemical staining of NADPH oxidase subunits gp91phox and p22phox were performed after 6 weeks′ treatment.Results Telmisartan treatment improved glucose tolerance,insulin secretion and insulin sensitivity,and remarkably decreased the staining intensity of the oxidative stress sources including p22phox and gp91phox in islets.Conclusion Telmisartan treatment can decrease the expression level of NADPH oxidase in β-cells,reduce oxidative stress sources,and thus protect β-cells.

关 键 词：糖尿病 胰岛 NADPH氧化酶 氧化应激 替米沙坦 

分 类 号：R587.1[医药卫生—内分泌]