中叶素对自发性高血压大鼠血管内皮功能的影响

Effects of intermedin on aorta endothelial functions of spontaneously hypertensive rats

目的研究中叶素对自发性高血压大鼠(SHR)血管内皮功能障碍的保护作用及其机制。方法 16只16周龄雄性清洁级SHR随机分为高血压对照组(SHR组)和中叶素1-53作用组(IMD组),每组各8只,另选8只WKY大鼠为非高血压对照组(WKY组)。IMD组皮下给予中叶素1-53[20nmol/(kg·d)],WKY组和SHR组给予生理盐水1.5mL/d,4周后取大鼠主动脉血管环,检测内皮依赖及内皮非依赖性舒张反应,同时测定大鼠体内氧化应激及一氧化氮/内皮型一氧化氮合酶(eNOS)水平。结果中叶素处理明显改善SHR主动脉内皮依赖性舒张反应,并使大鼠主动脉p22phox蛋白表达及超氧阴离子产生较SHR组分别降低38%和40%(均P<0.01),同时增强血浆抗氧化酶:超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)的活性。此外,中叶素处理可使SHR血浆一氧化氮产生及主动脉磷酸化eNOS蛋白表达分别增加89%和59%(P<0.01)。结论中叶素处理可改善SHR内皮功能障碍,该作用可能与中叶素抑制SHR体内氧化应激及增强血管eNOS活性有关。

Objective To investigate the protective effects of intermedin（IMD） on endothelial dysfunction in spontaneously hypertensive rats （SHR） and its mechanisms. Methods Sixteen 16-week-old male SHR were randomly divided into hypertensive control group （SHR group, n^8} and IMD1-53 treated group （IMD group, n=8}. Eight Wistar-Kyoto （WKY} rats served as non-hypertensive control group （WKY group}. The rats in IMD group were subcutaneously administered with IMD1-53 （20 nmol/（kg · d}. And the rats in SHR group and WKY group were subcutaneously injected with equal volume of normal saline （1.5 mL/d}. After four weeks of treatment, the endo- thelium-dependent and endothelium-independent relaxation response in rat aortic rings were measured, and the levels of oxidative stress, nitric oxide （NO}, and endothelial nitric oxide synthase{ NOS} in the serum were determined. Results The aortic endothelium-dependent relaxation response in IMD group was significantly ameliorated by IMD infusion. Compared with those of the SHR group, the levels of p22phox protein expression and superoxide anion in aortas of IMD group were reduced by 38 % and 40 % respectively { all P〈0. 01}, and the activation of superoxide dismutase （SOD}, catalase {CAT} and glutathione peroxidase （GSH-Px} in the serum was enhanced. Furthermore, compared with those of the SHR group, the NOx production level in the serum and the phosphorylated-eNOS ex pression in aortas of IMD group were respectively increased by 89% and 59% （P〈0. 01}. Conclusion IMD can improve endothelial dysfunction in SHR, which may be related to inhibit the oxidative stress and the activation of endothelial nitric oxide synthase.