坎地沙坦对自发性高血压大鼠骨骼肌核转录因子-2表达和胰岛素敏感性的影响  

Effects of candesartan on the expression of Nrf2 and insulin sensitivity in the spontaneous hypertension rats

作　　者：李凡[1] 谢静[1] 郝华[1] 黄慧[1] 曾强[1] 

机构地区：[1]解放军总医院国际医学中心,北京100853

出　　处：《中国临床保健杂志》2015年第2期182-184,I0001,共4页Chinese Journal of Clinical Healthcare

基　　金：北京市自然科学基金项目(7122171)

摘　　要：目的研究坎地沙坦对自发性高血压大鼠骨骼肌核转录因子-2(Nrf2)表达和胰岛素敏感性的影响。方法 30只自发性高血压大鼠随机分为对照组(C组)、模型组(M组)、坎地沙坦低剂量组(Can1组)、坎地沙坦高剂量组(Can2组),10只WKY大鼠作为对照组,均给予果糖喂养,Can1组及Can2组分别给予坎地沙坦(0.4mg/kg、0.8mg/kg)灌胃干预。实验第8周末,检测各组大鼠胰岛素抵抗指数(HOMA-IR)、血管紧张素Ⅱ(AngⅡ)、活性氧(ROS)以及Nrf2的表达水平。结果与C组相比,M组HOMA-IR水平及ROS表达显著升高,而Nrf2表达降低,差异有统计学意义(P<0.05、P<0.01);与M组相比,Can2组的ROS生成减少,HOMA-IR下降,差异有统计学意义(P<0.05、P<0.01);Can1及Can2组的Nrf2表达均较M组显著增加,差异有统计学意义(P<0.05、P<0.01)。结论坎地沙坦可以通过拮抗AngⅡ减轻AngⅡ诱导的骨骼肌胰岛素抵抗和氧化应激。Objective To investigate the effects of candesartan on the expression of Nrf2 and insulin sensitivity of the spontaneouslyhypertensive rats（SHR） and its possible mechanism.Methods 30 SHR were randomly divided into model group,low dose group andhigh dose group.10 WKY rats served as control group.All the rats fed with fructose,while the low andhigh dose group rats accepted candesartan consecutive treatment with the dose of 0.4mg/kg and 0.8mg/kg respectively.At the 8th weekend,the insulin resistance index（HOMA-IR）,the level of reactive oxygen species（ROS） and the expression of Nrf2 were detected.Results Compared with the control group,the HOMA-IR was significantly increased in the model group（P 0.05）,the protein expression of Nrf2 in model group significantly decreased（P 0.01） at the same time while the level of ROS increased significantly（P 0.01）.Compared with the model group,the HOMA-IR decreased obviously in thehigh dose group（P 0.01）.The protein expression of Nrf2 in the low dose andhigh dose group increased significantly（P 0.01,P 0.05） compared with model group,and the level of ROS significantly decreased compared with the model group（P 0.05）.Conclusion Candesartan could improve the insulin resistance and oxidative stress by the antagnism effect of AngⅡ in the skeletal muscle cells.

关 键 词：高血压 血管紧张素Ⅱ 胰岛素抗体 活性氧 大鼠 近交SHR 

分 类 号：R544.1[医药卫生—心血管疾病]