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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

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【作者】 赵春霞王家宁赵荫涛汪培华汪道文

【Author】 ZHAO Chun-xia,WANG Jia-ning,ZHAO Yin-tao,WANG Pei-hua,WANG Dao-wen Cardiovascular Division of Internal Medicine Department and Gene Therapy Center,Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430030,China

【机构】 华中科技大学同济医学院附属同济医院心内科华中科技大学同济医学院附属同济医院心内科 湖北武汉430030湖北武汉430030

【摘要】 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。

【Abstract】 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. ResultsFructose-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 mIu/L,P<0.05) after 3 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.

【基金】 国家自然科学基金资助项目(NO.30270561,30470824)
  • 【文献出处】 高血压杂志 ,Chinese Journal of Hypertension , 编辑部邮箱 ,2005年12期
  • 【分类号】R544.1
  • 【被引频次】4
  • 【下载频次】230
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