贝那普利对老龄自发性高血压大鼠血管糖基化终末产物形成及血管损伤的抑制

The Repressive Effects of Benazepril on the Formation of Advanced Glycosylation end Products and Vessel Injury in Old Spontaneously Hypertensive Rats

目的:探讨血管氧化应激与糖基化终末产物(AGEs)水平及其受体(RAGE)以及核逆转录因子-Kappa B(NF-κB)等在高血压血管损伤进程中的变化及贝那普利对其损伤路径的影响。方法:选30周龄自发性高血压大鼠随机分为自发性高血压大鼠组、贝那普利组[10 mg/(kg·d)]各12只及WKY组12只。贝那普利干预12周后,分别用放射免疫测定血浆激素水平、免疫组化或免疫荧光及RT-PCR检测血管AGEs、RAGE、NF-κB p65、NADPH氧化酶p47phox的表达。结果:3组之间血浆肾素活性差异无统计学意义(P>0.05)。贝那普利组血浆血管紧张素Ⅱ水平明显低于自发性高血压大鼠组(P<0.05)。免疫荧光和免疫组化检测显示贝那普利组血管AGEs和RAGE表达显著低于自发性高血压大鼠组。RT-PCR检测显示贝那普利组血管RAGE、NF-κB p65、还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶p47phox的mRNA表达明显低于自发性高血压大鼠组(P<0.01)。结论:①高血压病中血管紧张素Ⅱ促使血管内皮细胞AGEs与RAGE结合增加及NF-κB活化,是加速血管老化及血管重塑因素之一;②贝那普利能通过抑制AGE和RAGE通路及NF-κB活化,改善高血压血管重塑。

Objectives ：The aim of this study was to explore the changes of the vessel oxidation stress and the advanced glycosylation end products（ AGEs）, its receptor RAGE and nuclei transcription factor-KappaB （NF-κB）level during the vessel injury in spontaneously hypertensive rats（SHR）. We also studied the effects of benazepril on the injury route. Methods：The spontaneous hypertension rats at thirty weeks old were divided into the SHR group, benazepril （10 mg/（ kg · d） ） group and WKY group. After treatment for twelve weeks, the activity of plasma renin activity and angiotensin II level was assayed with by immunoradiometric assay. Their vascular accumulation of AGEs, expression of RAGE, component of NAPDH oxidase p47phox, NF-κB p65 were determined by immunofluorescence or immunohistochemistry, and RT-PCR. Results ： There were no significant differences in plasma renin activity among the different groups （ P 〉 0. 05 ）, but the level of blood plasma angiotensin II was higher in the SHR group than that in benazepril group（ P 〈 0. 05 ）. The expression of AGEs and RAGE in vessels in benazepril and WKY group were remarkably lower than those in the SHR group（ P 〈 0. 01 ）by immunofluorescence and immunohistochemistry analyses. The RT-PCR results showed that the expression levels of RAGE mRNA,NF-KBp65 mRNA and nicotinamide-adenine dinucleotide phosphate （ NADPH ） oxidase p47phox mRNA were inhibited by benazepril （ P 〈0.01）. Conclusions ： Angiotensin II promoted thebinding of endothelial AGEs and its receptor RAGE and increased the NF-κB activity in SHR. The vascular senility and remodeling were accelerated by AGE-RAGE route. Benazepril could improve the vascular remodeling by inhibition of the level of AGEs and the activities RAGE and NF-KB.