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

摘要

Objective To investigate the effects of candesartan on the expression of Nrf2 and insulin sensi-tivity of the spontaneously hypertensive rats(SHR)and its possible mechanism.Methods 30 SHR were randomly di-vided into model group,low dose group and high dose group.10 WKY rats served as control group.All the rats fed with fructose,while the low and high dose group rats accepted candesartan consecutive treatment with the dose of 0.4 mg/kg and 0.8 mg/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 HO-MA-IR was significantly increased in the model group(P <0.05),the protein expression of Nrf2 in model group sig-nificantly 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 the high dose group (P <0.01).The protein expression of Nrf2 in the low dose and high 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 AngⅡin the skeletal muscle cells.%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（0．4 mg／kg、0．8 mg／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。