论文部分内容阅读
目的探讨自发性高血压大鼠肾脏AGEs-RAGE系统、信号转导系统及细胞因子水平的变化,并研究贝那普利对其的影响。方法将24只SHR随机分为对照组(SHR组)和贝那普利组,12只Wistar京都大鼠为WKY组。SHR组和WKY组每天用等量蒸馏水灌胃1次;贝那普利组将贝那普利[10 mg/(kg.d)]研成粉末,加等量蒸馏水每天灌胃1次,12周后测定肾皮质Ang II水平及24 h尿蛋白,计算肾小球硬化指数;检测肾脏晚期糖基化终末产物(AGE)、VCAM-1、NF-κB及NADPH oxidase p47phox的表达。结果与WKY组比较,SHR组肾皮质Ang II水平及24 h尿蛋白、肾小球硬化指数显著升高(P<0.01),AGE、VCAM-1、NF-κB及NADPH oxidase p47phox的表达显著增强(P<0.01);与SHR组比较,贝那普利组肾皮质Ang II水平及24 h尿蛋白、肾小球硬化指数显著降低(P<0.01),AGE、VCAM-1、NF-κB及NADPH oxidase p47phox的表达显著减弱(P<0.01)。结论高血压肾脏氧化应激反应增强,AGEs与RAGE结合使NF-κB活化,增加VCAM、NADPH oxidase p47phox的表达,加速肾脏损害。贝那普利通过抑制氧化应激及AGEs表达,进一步抑制NF-κB及生长因子的表达,改善高血压肾脏损害。
Objective To investigate the changes of AGEs-RAGE system, signal transduction system and cytokines in spontaneously hypertensive rats and to study the effects of benazepril on it. Methods Twenty-four SHRs were randomly divided into control group (SHR group) and benazepril group, and 12 Wistar Kyoto rats as WKY group. The rats in SHR group and WKY group were orally administered with equal volume of distilled water once a day. The benazepril group was benazepril [10 mg / (kg · d)], and the same dose of distilled water was given to stomach once a day for 12 The renal cortex Ang II level and 24 h urinary protein were measured and the index of glomerulosclerosis was calculated. The expression of advanced glycation end products (AGE), VCAM-1, NF-κB and NADPH oxidase p47phox in kidney were detected. Results Compared with WKY group, the renal cortex Ang II level, 24 h urinary protein and glomerular sclerosis index in SHR group were significantly increased (P <0.01), and the expressions of AGE, VCAM-1, NF-κB and NADPH oxidase p47phox were significantly increased (P <0.01) .Compared with SHR group, renal cortex Ang II level, 24 h urinary protein and glomerular sclerosis index in benazepril group were significantly lower (P <0.01), AGE, VCAM-1, NF- The expression of NADPH oxidase p47phox was significantly attenuated (P <0.01). Conclusion The oxidative stress response in hypertensive kidney is enhanced. The combination of AGEs and RAGE activates NF-κB, increases the expression of VCAM and NADPH oxidase p47phox and accelerates renal damage. Benazepril further inhibits the expression of NF-κB and growth factor, and improves renal damage in hypertension by inhibiting oxidative stress and AGEs expression.