二氟甲基鸟氨酸对大鼠糖尿病心肌病氧化应激和自噬的影响  

Effects of difluoromethylalanine on oxidative stress and autophagy in diabetic cardiomyopathy rats

作　　者：林岩[1] 王珺 肖薇[1] 李波[1] 金莉[1] 廉洁[1] 于水 LIN Yan;WANG Jun;XIAO Wei;LI Bo;JIN Li;LIAN Jie;YU Shui(School of Basic Medicine,Qiqihar Medical University,Qiqihar 161006,Heilongjiang Province,China)

机构地区：[1]齐齐哈尔医学院基础医学院

出　　处：《中国临床药理学杂志》2019年第20期2559-2562,共4页The Chinese Journal of Clinical Pharmacology

基　　金：黑龙江省教育厅面上基金资助项目(2016-KYYWF-0846)

摘　　要：目的研究外源性给予二氟甲基鸟氨酸(DFMO)对大鼠糖尿病心肌病的氧化应激作用以及自噬相关因子的影响。方法按照体重将Wistar大鼠随机分为3组:正常组、模型组和实验组,每组10只。高糖高脂膳食和链脲佐菌素腹腔注射制备大鼠糖尿病模型。实验组给予糖尿病大鼠2%DFMO水溶液连续饮用12周。用实时荧光定量PCR法测定心房钠尿肽(ANP)基因表达水平;试剂盒法测定心肌组织谷胱甘肽过氧化物酶(GSH-Px)的活性,免疫印迹法检测自噬相关基因(ATG)蛋白表达水平。结果正常组、模型组和实验组ANP基因相对表达量分别为0. 75±0. 12,1. 31±0. 34和1. 06±0. 35;正常组、模型组和实验组GSH-Px活性分别为(178. 31±16. 21),(132. 56±15. 06),(150. 43±14. 22) U·mg^-1;正常组、模型组和实验组的ATG蛋白表达量分别为0. 23±0. 08,0. 95±0. 14和0. 64±0. 12。上述指标:模型组与正常组相比,差异均有统计学意义(P <0. 05或P <0. 01);实验组与模型组相比,差异均有统计学意义(P <0. 05或P <0. 01)。结论 DFMO减轻糖尿病心肌病大鼠的心肌肥厚与心肌纤维化程度,这可能与改善氧化应激和自噬有关。Objective To investigate the effects of difluoromethylornithine( DFMO) on oxidative stress and protein expression of autophagy related factors in diabetic cardiomyopathy rats. Methods Wistar rats were randomly individed into three groups: normal group,model group and experimental group,each group had 10 rats. The type 2 diabetic melitus rat model was induced by 4 weeks’ high sucrose-high fat diet feeding and one-time intraperitoneal injection of streptozotocin. Model rats in experimental group were treated with 2% DFMO drinking for 12 weeks. The gene expression of atrial natriuretic peptide( ANP) was detected by real time fluorescence quantitative-PCR. The activities of glutathion peroxide( GSH-PX) was determined by kit. The protein expression of autophagy related gene( ATG) was measured by Western blot. Results The gene expression of ANP in normal group,model group and experimental group were 0. 75 ± 0. 12,1. 31 ± 0. 34,1. 06 ± 0. 35,respectively;the activity of GSH-PX in normal group,model group and experimental group were( 178. 31 ± 16. 21),( 132. 56 ± 15. 06),( 150. 43 ± 14. 22) U·mg^-1,respectively;the protein expression of ATG in normal group,model group and experimental group were 0. 23 ± 0. 08,0. 95 ± 0. 14,0. 64 ± 0. 12,respectively. Comparing between model group and normal group,the difference were significant( P < 0. 05 or P < 0. 01);comparing between experimental group and model group,the difference of the above factors were significant( P < 0. 05 or P < 0. 01). Conclusion DFMO exerts protective effects on diabetic cardiomyopathy in T2 DM rats which may be related to its function on the downregulation of protein expression of ATG and inhibition of oxidative stress.

关 键 词：糖尿病心肌病 氧化应激 自噬 二氟甲基鸟氨酸 

分 类 号：R97[医药卫生—药品]