肾血管性高血压大鼠肠系膜动脉内皮细胞型一氧化氮合酶磷酸化变化的研究

The decrease of eNOS phosphorylation in mesenteric arteries of renovascular hypertension rats

目的在肾血管狭窄诱发高血压大鼠模型上,探讨肾血管性高血压大鼠肠系膜动脉内皮型一氧化氮合酶(eNOS)磷酸化变化的机制。方法 24只雄性大鼠随机分为假手术组和手术组,每组又分为2周组和4周组(n=6)。手术组采用双肾双狭的方法复制大鼠慢性肾血管性高血压模型,Westernblot印迹法检测肠系膜动脉eNOS蛋白的表达、eNOS丝氨酸(Ser1179)位点磷酸化水平以及磷酸酶2Ac(PP2Ac)的表达。硝酸还原酶法检测血浆一氧化氮(NO)的水平。结果与假手术组相比,双肾双狭高血压大鼠4周后肠系膜动脉eNOS蛋白表达、eNOSSer1179磷酸化水平明显降低,分别为42%和64%,PP2Ac蛋白水平明显增加(P均<0.05)。血浆NO水平在2周、4周时均明显降低(P<0.05)。结论肾血管性高血压大鼠肠系膜动脉eNOS总蛋白表达降低,同时eNOSSer1179磷酸化明显减弱,导致血浆NO水平降低,促进高血压的发生发展;而且PP2Ac水平升高可能是eNOSSer1179磷酸化水平降低的机制之一。

Objective To investigate the mechanisms of endothelial nitric oxide synthase(eNOS) phosphorylation changes in mesenteric arteries with renovascular hypertensive rats.Methods The chronic renovascular hypertensive rats was induced by 2-kidney,2-clip(2k2c).The expression of eNOS protein,the phosphorylation of eNOS at Ser1179 and the PP2Ac protein levels was assessed by Western blot.The level of nitric oxide(NO) in plasma was measured via NO assay.Results In mesenteric arteries,the levels of eNOS protein and the phosphorylation of eNOS Ser1179 were decreased(42% and 64%) after 4-week of 2k2c hypertensive rats compared with sham-operated group,while the expression of PP2Ac was increased compared with sham-operated group(all P < 0.05).The production of NO in plasma was decreased after 2 and 4 weeks of 2k2c groups compared with shamoperated group(both P < 0.05).Conclusions The level of NO is decreased in plasma may be caused by reduced in eNOS protein and phosphorylation of eNOS at Ser1179 of rats with renovascular hypertension.This may aggressive hypertension.Moreover,one of the mechanisms of decreased eNOS phosphorylation at Ser1179 is probably the increased PP2Ac.