胰岛素抵抗大鼠血压升高机制的实验研究

Experimental study on the mechanisms underlying blood pressure elevation in insulin-resistant rats

目的:探讨胰岛素抵抗大鼠模型血压升高的机制。方法:通过给予高糖饮食及NG-硝基-左旋-精氨酸-甲基酯(L-NAME)喂养建立不同的胰岛素抵抗大鼠模型,观察大鼠血压及血清内皮型一氧化氮合成酶(eNOS)、一氧化氮(NO)、超氧化物歧化酶(SOD)、超氧阴离子(O2-)和血浆血管紧张素Ⅱ(AngⅡ)的变化。结果:实验前各组大鼠血压差异无统计学意义(P>0.05),而实验4周时,高糖组、L-NAME组的血压均明显高于对照组(均P<0.01)。高糖组(P<0.05)和L-NAME组(P<0.01)NO水平均低于对照组,而O2-升高(均P<0.05)。L-NAME组的eNOS活性低于对照组(P<0.05),高糖组与对照组相比,差异无统计学意义(P>0.05)。与对照组相比,高糖组大鼠血清SOD活性明显降低(P<0.01)。各组大鼠AngⅡ水平与对照组相比差异无统计学意义(P>0.05)。结论:NO水平下降和氧化应激引起NO生物活性降低,在胰岛素抵抗大鼠模型高血压的发病机制中发挥重要作用。

Objective： To study the mechanisms underlying blood pressure elevation in insulin-resistant rats. Method：We established different insulin-resistant animal models by feeding rats with sucrose-rich diet （SRD） and Nomega-nitro-L-argininne-methylester （L-NAME） respectively. Then blood pressure, serum nitric oxide （NO）, endothelial NO synthase （eNOS）, superoxide dismutase（SOD）, superoxide anion （O2^- ） and plasma angiotensin Ⅱ （Ang Ⅱ ） of all rats were measured. Result：Both SRD and L-NAME rats developed hypertension （P〈0.01, re spectivety）. The level of NO in SRD （P〈0.05） and L-NAME rats （P〈0.01） decreased. When compared with controls, there was an obvious elevation of O2^- in SRD and L-NAME groups（P〉0.05）, whereas a reduction of SOD was observed in SRD（P〈0.01）. The eNOS activity decreased in L-NAME（P〈0.01）. We also found there was no significant difference of angiotensin Ⅱ among these groups（P〉0. 05）. Conclusion： Decreased production of NO and oxidative stress leading to NO bioactivity reduction played an important role in the pathogenesis of hypertension in insulin-resistant rats.