文献类型：期刊文献

中文题名：红芪多糖对糖尿病心肌病db/db小鼠核因子2相关因子2信号通路的影响

英文题名：Effect of Hedysarum polybotrys polysacchcaide on NF-E2-related factor 2 signaling pathway in db/db mice with diabetic cardiomyopathy

作者：何流[1];金智生[1];张花治[1];王栋[1];王东旭[1];和彩铃[1]

第一作者：何流

机构：[1]甘肃中医药大学中医临床学院,兰州730000

第一机构：甘肃中医药大学中医临床学院

年份：2018

卷号：34

期号：15

起止页码：1839

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：CSTPCD;;北大核心:【北大核心2017】；CSCD:【CSCD2017_2018】；

基金：国家自然科学基金地区科学基金资助项目(81360538)

语种：中文

中文关键词：糖尿病心肌病;氧化应激;红芪多糖;信号通路;db/db小鼠

外文关键词：diabetic cardiomyopathy;oxidative stress;Hedysarum polybotrys polysacchcaide;signaling pathway;db/db mice

摘要：目的研究红芪多糖(HPS)对db/db小鼠糖尿病心肌病(DCM)心肌组织中抗氧化应激的作用。方法按随机数表法将db/db小鼠分为5组(每组12只):模型组、对照组和高、中、低3个剂量实验组。正常组为同月龄同背景非转基因db/m小鼠(12只)。于7周龄对小鼠灌胃给药,1次/天,连续灌胃8周。高、中、低3个剂量实验组分别给予HPS 200,100,50 mg·kg^(-1)灌胃(质量浓度为20 mg·m L^(-1));对照组灌胃4 mg·kg^(-1)罗格列酮70μg·m L^(-1);模型组和正常组灌胃等量0.9%Na Cl 0.2 m L·d^(-1)。连续干预8周。用生化法检测心肌组织中丙二醛(MDA)含量;用蛋白印迹法和反转录聚合酶链式反应检测小鼠心肌组织核因子2相关因子2(Nrf2)、Kelch样ECH相关蛋白1(Keap1)及还原性辅酶/醌氧化还原酶(NQO1)蛋白和mRNA的表达。结果给药8周后,正常组、模型组和中、高2个剂量实验组的Nrf2蛋白表达分别为1.33±0.07,0.19±0.06,0.66±0.06,1.12±0.06;模型组与正常组比较,差异有统计学意义(P<0.01);中、高2个剂量实验组与模型组比较,差异均有统计学意义(均P<0.01)。正常组、模型组和低、中、高3个剂量实验组的MDA含量分别为(4.74±0.36),(7.20±0.49),(7.08±0.57),(6.62±0.67),(5.80±0.52)nmol·mg^(-1),模型组与正常组比较,差异有统计学意义(P<0.01);高、中2个剂量实验组与模型组比较,差异均有统计学意义(均P<0.01)。mRNA表达与其相应的蛋白表达趋势一致。结论 HPS可能通过调控Keap1-Nrf 2信号通路改善db/db小鼠DCM心肌损伤。
Objective To observe the effect of Hedysarum polybotrys polysacchcaide（ HPS） on the suppression of oxidative stress in myocardial tissue in diabetes（ db/db） mice with diabetic cardiomyopathy（ DCM）.Methods Sixty db/db mice（ 7-week-old） were randomly divided into five groups： high-dose experimental group,middle-dose experimental group,low-dose experimental group（ 200,100,50 mg · kg^（-1） HPS）,control group（ 4 mg·kg^（-1） rosiglitazone） and model group（ 0. 9%Na Cl,gavege）; while 12 db/m mice（ 7-week-old） were used as normal group. The contents of malondialdehyde（ MDA） were detected by biochemical method after 8 weeks. Western blotting method and Reverse transcription polymerase chain reaction method were used to detect the expressions of Kelch-like ECH-associated protein 1（ Keap1）,NF-E2-related factor 2（ Nrf2）,reductive coenzyme/quinone oxidoreductase 1（ NQO1） protein and mRNA in myocardial tissue. Results After the treatment of HPS for 8 weeks,the expressions of Nrf 2 protein in normal group,model group,middle-dose experimental group,high-dose experimental groups were 1. 33 ± 0. 07,0. 19 ± 0. 06,0. 66 ± 0. 06,1. 12 ± 0. 06,compared with the normal group,the Nrf 2 protein level in model group was with statistical difference（ P 0. 01）; compared with the model group,the Nrf 2 protein levels in the middle-dose and high-dose experimental groups were with statistical difference（ all P 0. 01）. The MDA contents in normal group,model group,low-dose experimental group,middle-dose experimental group,and high-dose experimental group were（ 4. 74 ± 0. 36）,（ 7. 20 ± 0. 49）,（ 7. 08 ± 0. 57）,（ 6. 62 ± 0. 67）,（ 5. 80 ± 0. 52） nmol·mg^（-1）; compared with the normal group,MDA content of model group was with statistical difference（ P 0. 01）; compared with the model group,MDA contents of the middle-dose experimental group,and high-dose experimental group were with statistical difference（ all P 0. 01）.The expression of mRNA is consistent with its corresponding protein expression trend. Conclusion HPS can reduce the development of myocardial injure by controlling oxidative stress through the Keap1-Nrf 2 signaling pathway.