替米沙坦对db/db小鼠胰岛内氧化应激损伤的影响  

The Effects of Telmisartan on Intra-islet Oxidative Stress in db/db Mice

作　　者：顾萍[1] 邵加庆[1] 杜宏[1] 卢斌[1] 王扬天[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,江苏省南京市210002

出　　处：《中国全科医学》2010年第36期4107-4110,共4页Chinese General Practice

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

摘　　要：目的探讨替米沙坦阻断肾素-血管紧张素系统对db/db小鼠胰岛内氧化应激水平的影响。方法将22只8周龄db/db小鼠随机分为两组(替米沙坦组和db/db组),各11只,分别给予替米沙坦5 mg.kg-1.d-1和安慰剂。另选择11只同周龄db/m小鼠给予安慰剂灌胃作为非糖尿病对照组(db/m组)。每周监测小鼠的体质量、血糖,6周后行腹腔葡萄糖耐量试验并取胰腺行免疫组化,分析胰岛内氧化应激标记物——8-羟-2′-脱氧鸟苷(8-OHdG)及4-羟壬烯醛(4-HNE)的表达情况。结果投药6周后,替米沙坦组小鼠的血糖、胰岛素抵抗指数(IR I)、葡萄糖曲线下面积显著低于db/db组,胰岛素曲线下面积显著高于db/db组,差异有统计学意义(P<0.05)。与db/db组比较,替米沙坦组小鼠胰岛内的8-OhdG阳性率及4-HNE表达水平显著降低,差异有统计学意义(P<0.05)。结论替米沙坦阻断AT1受体能够改善胰岛微环境,降低8-OHdG、4-HNE的表达,减少氧化应激,从而保护胰岛β细胞。Objective To explore the effects of telmisartan on intra-islet oxidative stress in db/db mice.Methods Twenty-two db/db mice aged 8 weeks were randomized to telmisartan group and db/db group,fed with 5 mg·kg-1·d-1 telmisartan and placebo respectively.Eleven age-matched db/misty mice were concurrently treated with placebo as non-diabetic control group.Body weight and blood glucose were measured every week.After 6 weeks′ treatment,intraperitoneal glucose tolerance test and immunohistochemical staining were performed and the expression of 8-OHdG and 4-HNE were analyzed.Results Six weeks′ telmisartan treatment improved significantly the glucose tolerance,insulin secretory function and insulin resistance（P〈0.05）.And telmisartan treatment significantly decreased staining intensity of oxidative stress sources including 8-OHdG and 4-HNE in islets（P〈0.05）.Conclusion Telmisartan treatment remarkably decreases the expression level of 8-OHdG and 4-HNE in β-cells by improving pancreatic microenvironment,and prevents the damage from excess oxidative stress,thus protects β-cell function.

关 键 词：替米沙坦 糖尿病 氧化性应激 胰岛 8-羟-2′-脱氧鸟苷 4-羟壬烯醛 

分 类 号：R587.1[医药卫生—内分泌]