不同周龄自发性高血压大鼠血管内皮功能及氧化应激的变化研究

Endothelium function and oxidation stress in spontaneous hypertensive rats of different weeks of age

目的:观察不同周龄的自发性高血压大鼠(SHR)内皮功能变化、体内的氧化应激状态及其对血管内皮功能的影响。方法:将SHR随机分为3组:5周、16周及40周龄组,每组各15只。观察SHR离体胸主动脉和肾动脉对乙酰胆碱(Ach)的反应性,并对其内皮功能变化进行比较,分别使用放射免疫法、硝酸还原酶法、硫代巴比妥酸比色法和5,5′-二硫代双(2-硝基苯甲酸)(DTNB)法检测血中内皮素(ET)、一氧化氮(NO)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)含量。结果:内皮依赖性血管舒张功能随着周龄的增加而减弱。随着周龄的增加,血管活性物质NO/ET及氧化应激标志GSH-Px、MDA发生变化。16周及40周血清NO低于5周龄SHR[(12.84±1.58)μmol/L,(12.17±1.17)μmol/Lvs(22.64±1.69)μmol/L,P<0.01];16周及40周ET分泌水平无明显差别,与5周相比无显著差别;40周MDA含量[(13.71±1.47)ng/L]与5周[(7.54±1.19)ng/L]和16周[(7.94±0.83)ng/L]相比明显增加(P<0.01);而40周GSH-Px活力[(2 368.00±60.39)×103U/L]与5周[(2 925.00±75.11)×103U/L]和16周[(2 976.00±329.94)×103U/L]相比明显降低(P<0.01)。结论:SHR存在内皮功能损伤及氧化应激的增加,随着周龄的增加损伤加重。

AIM：To observe the endothelial function and oxidation stress in spontaneous hypertensive rats（SHR） of different weeks of age.METHODS：Endothelium-dependent vasodilation of exsomatized aorta thoracalis and renal artery in 5 week-,16 week-and 40 week-old SHR was observed and compared.Radioimmunoassay and the methods of nitrate reductase,thiobarbituric acid and 5,5′-dithiobis（2-nitrobenzoic acid） were used to measure the levels of endothelin（ET）,nitric oxide（NO）,malondialdehyde（MDA） and glutathione peroxidase（GSH-Px）,respectively.RESULTS：The results indicated that the endothelium-dependent vasodilation was weakened along with aging.Vasoactive substance such as NO/ET and the oxidized stress symbolized by GSH-Px or MDA were also changed along with aging.The level of serum NO in 16 and 40 week-old SHR were lower than that in 5 week-old SHR[（12.84±1.58） μmol/L and（12.17±1.17） μmol/L vs（22.64±1.69） μmol/L]（P〈0.01）.No significant difference of the ET level among the 3 groups was observed.The level of MDA[（13.71±1.47） ng/L] in 40 week-old animals was significantly higher than that in 5 week-old SHR[（7.54±1.19）ng/L] and 16 week-old SHR [（7.94±0.83） ng/L]（P〈0.01）.The activity of GSH-Px in 40 week-old SHR [（2 368.00±60.39）×103 U/L] was significantly lower than that in 5 week-old SHR [（2 925.00±75.11）×103 U/L] and 16 week-old SHR [（2 976.00± 329.94）×103U/L]（P〈0.01）.CONCLUSION：The damaged endothelial function and increased oxidation stress are existed in SHR and are aggratated with aging.