黄嘌呤氧化酶对血管内皮功能障碍的影响

Role of Xanthine Oxidase in Endothelial Dysfunction in Spontaneously Hypertensive Rats

目的考察黄嘌呤氧化酶(xanthine oxidase)在自发性高血压大鼠(SHR)血管舒缩及内皮功能障碍中的作用。方法采用尾套法测定SHR和正常大鼠(WKY)血压;Greiss反应测定血清一氧化氮分泌量;FRAP(ferric reduction abilitypower)法测定主动脉蛋白总抗氧化能力;RT-PCR法考察黄嘌呤氧化酶及内皮型一氧化氮合酶(eNOS)mRNA表达情况;血管环舒缩测定来评价黄嘌呤氧化酶抑制剂别嘌呤醇(oxypurinol,Oxy)对大鼠腹主动脉内皮依赖性舒张反应的影响。结果SHR血压(191.1±5.6)显著高于WKY大鼠(140.4±5.9)mmHg;SHR血清NO分泌量(28.4±5.4)、主动脉蛋白总抗氧化能力(1.02±0.14)U/μg蛋白和腹主动脉内皮依赖性舒张反应(66.2±4.6)%均显著低于WKY[分别为(51.6±5.8),(2.8±0.3)U/μgpro和81.0%±2.7%);而心、肾及主动脉中黄嘌呤氧化酶表达均显著高于WKY大鼠(P<0.05)。黄嘌呤氧化酶抑制剂Oxy能明显降低黄嘌呤氧化酶mRNA表达(降低31.6%),且改善腹主动脉内皮依赖型舒张反应(提高20.2%),但对eNOS表达则无显著影响。结论结果提示SHR中存在内皮功能障碍和氧化应激状态,黄嘌呤氧化酶参与了SHR内皮功能障碍。

Objective To investigate the role of xanthine oxidase in blood vessel contractility, endothelial dysfunction in spontaneously hypertensive rats （SHR）. Methods Systolic blood pressure in SHR and agematched Wister-Kyoto （WKY） normotensive rats were measured by tail-cuff method. Serum nitric oxide （NO） level and total antioxidant capacity （TAC） of aorta protein were evaluated by Greiss reaction and FRAP methods. Xanthine oxidase and endothelial nitric oxide synthase （eNOS） mRNA expressions were assayed with RT-PCR analysis. The effect of xanthine oxidase inhibitor, oxypurinol （D-2-methylmalic acid, Oxy）, on endothelium-dependent vasodilation was investigated using aorta rings. Results The SBP in SHR（191.1± 5.6 mm Hg） was significantly higher compared with that of WKY（ 140. 4±5.9 mm Hg）. In SHR, serum NO level （28. 4±5.4 vs 51.6±5. 8μmol/L, P〈0.05） ; vascular tissue protein TAC （1.02±0.14 vs 2.8±0. 3 U/μg pro, P〈0.05） ; and the endothelium-dependent vasodilation （66.2 % ± 4.6 % vs 81.0 % ± 2. 7 % ） were markedly decreased comparing with those of WKY. Xanthine oxidase mRNA expression in heart, kidney, and aorta of SHR were greatly enhanced than those of WKY （P〈0. 05 ）. Treatment of xanthine oxidase inhibitor Oxy down regulated mRNA expression of xanthine oxidase by 31.6 %, and restored attenuated endothelium-dependent vasodilation of SHR by 20. 2% while no influence on aortic eNOS mRNA expression was found. Conclusion Endothelial dysfunction and oxidative stress were shown significantly in SHR. Xanthine oxidase-derived oxidative stress may play role in the endothelial dysfunction of SHR.