艾塞那肽对1型糖尿病大鼠肾脏NADPH氧化酶亚单位表达的影响  

Effect of GLP-1 on the expression of NADPH oxidase subunits in the kidney of type 1 diabetic rats

作　　者：刘晋津[1] 郭志新[1] 齐伟[1] 吴杰萍[1] 杜时晶[1] 俞媛贤[1] 

机构地区：[1]山西医科大学第二医院内分泌科,太原030001

出　　处：《解放军医学杂志》2013年第9期720-724,共5页Medical Journal of Chinese People's Liberation Army

基　　金：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(01201015);山西省自然科学基金(2013011047–1);山西省留学人员科技活动择优资助项目(2012)~~

摘　　要：目的观察胰高血糖素样肽1(GLP-1)受体激动剂艾塞那肽对链脲佐菌素(STZ)诱导的1型糖尿病大鼠肾脏NADPH氧化酶亚单位NOX4和p22phox,以及结缔组织生长因子(CTGF)表达的影响,探讨艾塞那肽对糖尿病大鼠肾脏的保护作用及其机制。方法 30只雄性SD大鼠随机分为正常对照组(A组,n=7)和糖尿病造模组(n=23)。采用STZ诱导1型糖尿病大鼠模型,共有19只大鼠造模成功。将造模成功的糖尿病大鼠随机分为糖尿病对照组(B组,n=10)和艾塞那肽治疗组(C组,n=9)。C组予以艾塞那肽5μg/kg,2次/d皮下注射,A组和B组给予等量生理盐水皮下注射。艾塞那肽治疗8周后放血处死动物,测定血生化指标及尿白蛋白排泄率,并计算肾脏指数,采用实时荧光定量PCR法测定肾脏NOX4和p22phox mRNA的表达,免疫组化法检测肾脏组织CTGF蛋白的表达及分布。结果与A组比较,B组糖尿病大鼠血糖、血脂、血肌酐、尿素氮、尿白蛋白排泄率、肾脏指数、肾脏NOX4和p22phox mRNA以及CTGF蛋白表达均显著升高(P<0.05)。经艾塞那肽治疗后,大鼠血脂、血肌酐、尿素氮、尿白蛋白排泄率、肾脏指数、肾脏NOX4和p22phox mRNA以及CTGF蛋白表达显著降低(P<0.05),但血糖与B组比较无明显变化(P>0.05)。结论艾塞那肽可使1型糖尿病大鼠肾脏NOX4、p22phox和CTGF表达降低,尿蛋白减少,肥大减轻,对肾脏有保护作用。Objective To observe the effect of exenatide,a glucagon-like peptide-1（GLP-1） receptor agonist,on the expression of NADPH oxidase subunits NOX4 and p22phox and connective tissue growth factor（CTGF） in the kidney of streptozotocin（STZ）-induced type 1 diabetic rats,and explore the protective effects and mechanisms of exenatide on the kidney of diabetic rats.Methods Thirty male Sprague-Dawley（SD） rats were divided into control group（group A,n=7） and diabetic model group（n=23）.Type 1 diabetic model was reproduced by intraperitoneal injection of streptozotocin.It was successful in 19 rats.Diabetic rats were randomly divided into diabetic control group（group B,n=10） and diabetic with treatment of exenatide group（group C,n=9）.Rats in group C were injected subcutaneously with exenatide in dose of 5μg/kg twice daily.Rats in group A and B were given equivalent volume of normal saline by subcutaneous injection.All rats were sacrificed after eight weeks.The mRNA expression of renal p22phox and NOX4 were detected by real-time fluorescence quantitative PCR.The protein expression of CTGF was detected by immunohistochemical staining.Results The levels of blood glucose,lipids,creatinine,and urea nitrogen,the albumin excretion rate,kidney index,the mRNA expressions of renal NOX4 and p22phox,and the protein expression of renal CTGF were significantly increased in group B compared with that in group A（P0.05）.After exenatide treatment,the blood lipids,creatinine and urea nitrogen,the albumin excretion rate,kidney index,the expression of renal NOX4 and p22phox,and the protein expression of renal CTGF were significantly decreased in group C compared with that in group B（P0.05）.No significant difference was found in the level of blood glucose between group B and group C（P0.05）.Conclusion Exenatide can decrease the expressions of renal NOX4,p22phox and CTGF,decline the index of urinary protein,and alleviate the kidney hypertrophy in type 1 diabetic rats,implying that exenatide exerted a protec

关 键 词：胰高血糖素样肽1 糖尿病肾病 NADPH氧化酶 氧化性应激 

分 类 号：R587.1[医药卫生—内分泌]