果糖诱导高血压大鼠血管内皮素-1、内皮素受体-A和内皮源性一氧化氮合酶表达的变化

Vascular Endothelin-1 and Endothelin-A Receptor and Endithelial Nitric Oxide Synthase in Fructose-induced Hypertensive Rat Model

目的研究果糖诱导高血压和胰岛素抵抗大鼠血管内皮素-1(ET-1)及内皮素-A受体(ETA-R)和内皮源性一氧化氮合酶(eNOS)的变化,探讨内皮功能变化在果糖诱导高血压和胰岛素抵抗中的作用。方法雄性Sprague-Dawley(SD)大鼠饮用10%果糖水3周,尾套法测量血压,并留取血清及尿标本分别测定血清胰岛素、血脂、血糖及血和尿中血ET-1水平后,处死大鼠。ELISA法测定血清及尿中ET-1水平,RT-PCR法测定大鼠主动脉中ET-1及ETA-R表达,Western杂交检测eNOS的表达情况。结果与正常饮水大鼠相比,高果糖饮水3周后,大鼠血压明显升高[(132.8±1.49 vs 120.5±1.7)mmHg,P<0.01]、血胰岛素水平亦明显高于正常饮水组[(12.2±2.3 vs 9.5±1.2)mIu/L,P<0.05]。两组间血清ET-1的水平并没有显著差异,但尿中ET-1的水平,果糖饮水组显著高于正常对照组。果糖饮水组大鼠主动脉ET-1和ETA-R的mRNA水平明显升高,而eNOS蛋白质水平显著低于正常组。结论ET-1和ETA-R高表达及eNOS表达的降低参与了果糖诱导高血压和高胰岛素血症的形成。

Objective To examine the vascular of endothelin-1（ET-1 ）, endothelin-A receptor（ETA R） and endithelial nitric oxide synthase （eNOS） in fructose-induced hypertension and hyperinsulinemia rats. Methods Male Sprague-Dawley rats fed on high-fructose （ 10% ） water developed mild hypertensive models within 3 weeks. Blood glucose, insulin and ET-1 were determined. Vascular ET-1 and ETA-R gene expressions were measured by RT-PCR. The expression of vascular eNOS was measured by Western blot. Results Fructose-fed rats developed systolic hypertension （ 132.8 ± 1.5 vs 120.5±1.7 mm Hg, P〈0.01） and hyperinsulinemia （12.2±2.3 vs 9.5±1.2 mlu/L, P〈0.05） after3 weeks. Although plasma ET-1 levels did not differ between the rat groups, urine ET-1 levels were significantly higher in fructose fed rats than in controls. Fructose-fed rats had higher vascular ET-1 and ETA-R gene expression than that in control rats, associated with lower level of eNOS was also shown. Conclusion These findings suggest that elevated vascular expression of ET-1 and ETA-R and the lower eNOS genes may mediate the development of hypertension and hyperinsulinemia in rats fed a fructose-rich diet.