新型肠促胰岛素类似物对糖尿病脑缺血再灌注大鼠氧化应激损伤的影响  

Effect of DA3-CH on oxidative stress injury in diabetic and cerebral ischemia/reperfusion rats

作　　者：韩玉迪 李东芳[1] 白波[1] 王美琴 Han Yudi;Li Dongfang;Bai Bo;Wang Meiqin(Department of Neurology,Shanxi Medical University No.2 Hospital,Taiyuan 030000,Shanxi Province,China)

机构地区：[1]山西医科大学第二医院神经内科,太原030000

出　　处：《中华老年心脑血管病杂志》2021年第11期1205-1208,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：山西省自然科学基金(201801D121213)。

摘　　要：目的研究新型胰高血糖素样肽1和葡萄糖依赖性促胰岛素分泌多肽双受体激动剂(DA3-CH)是否可通过激活核因子E2相关因子2(Nrf2)/抗氧化反应元件(ARE)通路减轻糖尿病脑缺血再灌注大鼠的氧化应激损伤。方法选取SPF级雄性SD大鼠36只,随机选取24只进行糖尿病造模后分为模型组和DA3-CH组,其余12只为空白组(n=12)。模型组和DA3-CH组制备脑缺血再灌注模型,DA3-CH组腹腔注射DA3-CH。检测各组改良神经功能缺损评分(mNSS),Nrf2、血红素加氧酶1(HO-1)和醌氧化还原酶1(NQO1)蛋白表达,超氧化物歧化酶(SOD)活性及丙二醛水平。结果与空白组比较,模型组和DA3-CH组血糖、mNSS、脑梗死面积、Nrf2、HO-1、NQO1蛋白表达及丙二醛水平升高,SOD活性降低(P<0.01)。DA3-CH组血糖、mNSS、脑梗死面积、丙二醛水平明显低于模型组[(21.50±1.52)mmol/L vs(24.53±2.53)mmol/L,(8.75±1.66)分vs(12.58±1.73)分,(12.35±3.68)%vs(39.43±3.05)%,(2.52±0.41)nmol/mg vs(4.69±0.43)nmol/mg,P<0.01];DA3-CH组Nrf2、HO-1、NQO1蛋白表达及SOD活性明显高于模型组(P<0.01)。结论新型肠促胰岛素类似物DA3-CH可通过激活Nrf2/ARE通路减轻糖尿病脑缺血再灌注大鼠的氧化应激损伤。Objective To study whether DA3-CH can alleviate oxidative stress injury by Nrf2/ARE in diabetic and CIRI rats.Methods Of the 36 SPF male SD rats,24 were randomly selected to establish the DM model and divided into model group and DA3-CH group,and 12 served as a blank group(n=12).A CIRI model of rats was established for model group and DA3-CH group.The mNSS was recorded,the MDA level and SOD activity were measured,the expressions of Nrf2,HO-1,NQO1 proteins were detected.Results The area of cerebral infarction was significantly larger,the mNSS,serum levels of blood glucose and MDA,expression levels of Nrf2,HO-1,NQO1 were significantly higher while the SOD activity was significantly lower in model group and DA3-CH group than in blank group(P<0.01).The serum levels of blood glucose and MDA,mNSS,ratio of cerebral infarction area were significantly lower in DA3-CH group than in model group(21.50±1.52 mmol/L vs 24.53±2.53 mmol/L,8.75±1.66 vs 12.58±1.73,12.35%±3.68%vs 39.43%±3.05%,2.52±0.41 nmol/L vs 4.69±0.43 nmol/L,P<0.01)while the expression levels of Nrf2,HO-1,NQO1 proteins and SOD activity were significantly higher in DA3-CH group than in model group(P<0.01).Conclusion DA3-CH can alleviate oxidative stress injury by activating the Nrf2/ARE pathways in diabetic and CIRI rats.

关 键 词：肠促胰岛素类 氧化性应激 血红素加氧酶-1 超氧化物歧化酶 丙二醛 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R587.2[医药卫生—临床医学]