【摘要】 目的通过观察培哚普利(Perindopril)对高血压大鼠一氧化氮及血管内皮功能的影响,探讨其对高血压肾损害保护的可能机制。方法将正常血压大鼠(WKY)随机分为3个月龄(WKY3个月)、正常对照组和8个月龄正常对照组(WKY8个月);高血压大鼠(SHR)随机分为3个月龄非治疗组(SHR3个月)、8个月龄非治疗组(SHR8个月)、8个月龄Perindopril治疗组(SHR-P8个月)。测量各组大鼠24h尿白蛋白浓度、血清和肾组织一氧化氮(NO)浓度,并用电镜观察各组大鼠血管内皮和肾小球形态学改变。结果SHR3个月组大鼠电镜下已见血管内皮细胞增生,肾小球基底膜轻度增厚,与WKY3个月组相比血清和肾组织NO浓度均下降、尿白蛋白浓度增高;SHR8个月组大鼠血管内皮细胞显著增生,肾小球系膜细胞肥大,基底膜明显增厚,尿白蛋白水平增高更为明显;高血压大鼠尿白蛋白浓度与血清和肾组织NO浓度呈明显负相关,与血管内皮细胞体密度、肾小球系膜细胞体密度和肾小球基底膜厚度呈正相关。Perindopril组与SHR8个月对照组大鼠相比,尿白蛋白水平明显下降,血清和肾组织NO浓度增高,血管内皮细胞和系膜细胞体密度减小,肾小球基底膜厚度减小。结论Perindopril对高血压大鼠肾脏的保护,可能是通过提高血清和肾组织NO水平,改善肾脏血管内皮功能来实现的。更多还原

【Abstract】 【Objective】 To observe the effects of perindopril on nitric oxide and endothelial function in Spontaneously hypertensive rats (SHR), investigate the mechanisms of protective roles of the drug. 【Methods】Wistar-Kyoto Rats (WKY) were randomly divided into three-month old rats group and eight-month old rats group. SHR were randomly divided into three-month old rats group, eight-month old rats group and perindopril group. 24 hours urinary microalbumin and NO level were detected. Relevant ultrastructural indexes in vessel and glomerulus with transmission electronic microscope were acquired. 【Results】In three-month old SHR, electronic microscopic observation demonstrated early impairment of vessel endothelium and slight lesion of glomerular basement membrane compared withage-matched controls, the SHR had lower level of renal NO and elevation of microalbuminuria. At eight-month old, aggravation of impairment of vessel endothelium and lesion of glomerulus has been shown. Urinary microalbumin was negative correlation with NO level and positive correlation with lesion of endothelium and glomerulus. With the treatment of perindopril, not only reduction of urinary microalbumin was achieved but also elevation of NO and decrease in volume density of vessel endothelium, mesangial cells and mesangial area were shown.【Conclusions】Perindopril can inhibit the deteriorations of kidney of SHR by way of elevating NO level and improving endothelial function.更多还原