胰高血糖素样肽1对1型糖尿病大鼠心肌烟酰胺腺嘌呤二核苷酸氧化酶亚单位表达的影响  

Effects of glucagon-like peptide-1 on the expression of nicotinamide adenine dinucleotide phosphate oxidase subunits in the heart of type 1 diabetic rats

作　　者：俞媛贤[1] 郭志新[1] 齐伟[1] 杜时晶[1] 刘晋津[1] 吴杰萍[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：《中华糖尿病杂志》2013年第11期683-688,共6页CHINESE JOURNAL OF DIABETES MELLITUS

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资助项目（01201015）;山西省自然科学基金资助项目（2013011047-1）

摘　　要：目的 探讨胰高血糖素样肽1 （GLP-1）对1型糖尿病大鼠心肌组织烟酰胺腺嘌呤二核苷酸（NADPH）氧化酶亚单位p22phox和Nox4表达的影响.方法 将42只雄性SD大鼠用随机数字表法分为正常对照组（NC组,n=7）和糖尿病造模组（n=35）.采用链脲佐菌素（STZ）对糖尿病造模组制备1型糖尿病大鼠模型.将造模成功的29只1型糖尿病大鼠用随机数字表法分为糖尿病组（DM组,n=10）,糖尿病GLP-1低剂量治疗组（DL组,n=10）和糖尿病GLP-1高剂量治疗组（DH组,n=9）.DL组予以艾塞那肽1μg/kg,2次/d皮下注射,DH组予以艾塞那肽5μg/kg,2次/d皮下注射.艾塞那肽治疗8周后处死动物.用实时荧光定量聚合酶链反应测定4组大鼠心肌p22phox和Nox4 mRNA的表达,免疫组化法检测心肌铜-锌-超氧化物歧化酶（Cu-Zn-SOD）蛋白表达.多组比较采用单因素方差分析.结果 与NC组比较,DM组大鼠心肌p22phox和Nox4 mRNA表达显著升高（t=5.77、5.36,均P＜0.05）,心肌Cu-Zn-SOD蛋白表达显著升高（t=59.91,P＜0.05）.艾塞那肽治疗8周后,与DM组比较,DL组和DH组大鼠心肌p22phox和Nox4 mRNA表达均显著降低（t=16.86、7.66和16.11、7.59,均P＜0.05）,心肌Cu-Zn-SOD蛋白表达均显著降低（t=56.00、47.05,均P＜0.05）.与DL组比较,DH组大鼠心肌p22phox和Nox4 mRNA表达显著降低（t=10.14、8.67,均P ＜0.05）,而心肌Cu-Zn-SOD表达无明显变化（=81.91,P＞0.05）.结论 GLP-1可剂量依赖性地下调1型糖尿病大鼠心肌p22phox和Nox4的表达,非剂量依赖性地上调心肌Cu-Zn-SOD表达,减轻氧化应激对心肌的损害,对糖尿病大鼠心肌产生保护作用.Objective To explore the effect of glucagon-like peptide-1 on the expression of nicotinamide adenine dinucleotide phosphate （NADPH） oxidase subunits p22phox and Nox4 in the heart tissue of type 1 diabetic rats.Methods Forty-two male Sprague-Dawley（SD） rats were randomly divided into normal control group （group A,n=7） and diabetic model group （n =35） with the random number table.Type 1 diabetic model was established by intraperitoneal injection of streptozotocin.Twenty-nine successfully-induced diabetic rats were randomly divided into diabetic （group DM,n =10）,diabetic treated with low-dose of GLP-1 （group DL,n =10） and diabetic treated with high-dose of GLP-1 （group DH,n =9） with the random number table method.The rats in group DL were given exenatide in dose of 1 μg/kg twice daily by subcutaneous injection.The rats in group DH were given exenatide in dose of 5 μg/kg twice daily by subcutaneous injection.All rats were sacrificed after exenatide treatment for eight weeks.The mRNA expression of myocardial p22phox and Nox4 in the rats of four groups was detected by real-time fluorescence quantitative polymerase chain reaction（PCR）,and the protein expression of myocardial copper zinc-superoxide dismutase （Cu-Zn-SOD） was detected by immunohistochemical staining.Statistical analysis among groups was performed by using one way ANOVA.Results Compared with group NC,the mRNA expression of myocardial p22phox and Nox4 and the myocardial Cu-Zn-SOD protein expression increased significantly in group DM（t =5.77,5.36,59.91,all P ＜0.05）.After exenatide treatment for 8 weeks,the mRNA expression of myocardial p22phox and Nox4 and the myocardial Cu-Zn-SOD protein expression decreased significantly in group DL and DH （t =16.86,7.66 and 16.11,7.59 and 56.00,47.05,and all P ＜ 0.05）.Compared with group DL,the mRNA expression of myocardial p22phox and Nox4 decreased significantly in group DH （t =10.14,8.67,both P ＜ 0.05）.There was no significant difference in the expression of myoca

关 键 词：糖尿病 1型 糖尿病心肌病 胰高血糖素样肽1 

分 类 号：R587.1[医药卫生—内分泌]