L-NAME加剧自发性高血压大鼠肾脏硬化  

L-NAME-Exacerbated Nephrosclerosis in Spontaneously Hypertensive Rats

作　　者：夏春梅[1] 丁爽爽[1] 奚剑飞[1] 张周[1] 

机构地区：[1]中国科学院上海药物研究所,上海200031

出　　处：《上海实验动物科学》2003年第4期207-211,共5页Shanghai Laboratory Animal Science

摘　　要：应用L-NAME加剧自发性高血压大鼠(SHR)肾脏硬化的进程,建立高血压性慢性肾功能不全大鼠模型。按SHR体重随机分成对照组和实验组,在实验组大鼠饮水中加入硝基左旋精氨酸甲酯(L-NAME)50 mg/L,分别收集两组大鼠0、14、28 d的24 h尿液,用Breadford法测定尿蛋白的含量,并用牛血清蛋白作标准曲线。在收集完最后一次24 h尿样后进行心脏血流动力学和肾脏清除率实验,用半定量的评分方法进行肾脏病理学检查。结果发现,实验组大鼠的平均动脉压为175mmHg,左室舒张末期压为9.2 mmHg,均显著高于对照组。心率和左室压力上升的最大变化率(dP/dtmax)两组间无显著性差异,心脏和左心室有增生肥大。肾脏血流动力学结果显示,肾脏血管阻力升高,导致血浆流量减少,肾小球滤过率降低,滤过分数升高。L-NAME诱导蛋白尿进行性升高,病理检查结果表明,实验组肾小球硬化,肾小管间质和肾血管损害指数均显著高于对照组。实验证实,L-NAME可加剧自发性高血压大鼠(SHR)肾脏硬化进程。To evaluate whether N-nitro-L-arginine methylester (L-NAME) can exacerbate nephrosclerosis in spontaneously hypertensive rats (SHR), SHR were randomly divided into two groups according to their body weight. Group I (SHR, n = 10) were given tap-water, while Group II (SHR + NAME, n = 9) were received L-NAME in the drinking water (50 mg/L). Twenty-four-hour urine samples were collected at base line, weeks 2 and 4 after the start of L-NAME for proteinuria determination. Cardiac hemodynamic and renal clearance experiments were performed after the last 24 h urine collection. The severity of the renal injury was semi-quantitatively assessed. The results showed that the L-NAME in duced significant increases in mean arterial blood pressure and left ventricular end-diastolic pressure at the end of the treat-ment, but had little effects on heart rate and the maximal rate of rise of LV pressure (dP/ dtmax). It also induced significant rises in the ratios of heart weight/body weight and left ventri-cle weight/body weight. In the kidney, L-NAME induced a progressive increases in proteinuria. It caused a profound elevation in renal vascular resistance, leading to a marked decrease in renal plasma flow, but a proportionately lesser decline in GFR. Thus , the filtration fraction rose. Se-mi-quantitative histological lesion grading revealed severe tubulointerstitial and renal vascular le-sions, along with very mild glomerular sclerosis in SHR treated with L-NAME. Our results sug-gest that L-NAME exacerbated nephrosclerosis in SHR. Young SHR treated with L-NAME can be used as a model of chronic renal failure.

关 键 词：硝基左旋精氮酸甲酯 自发性高血压大鼠 血流动力学 血管阻力 肾脏硬化 高血压 

分 类 号：R544.1[医药卫生—心血管疾病] Q95-33[医药卫生—内科学]