Gava Agata L, Freitas Flavia Ps, Balarini Camille M, Vasquez Elisardo C, Meyrelles Silvana S
Laboratory of Transgenes and Cardiovascular Control, Physiological Sciences Graduate Program, Health Sciences Center, Federal University of Espirito Santo Vitoria, ES, Brazil ; Biotechnology Graduate Program, Health Sciences Center, Federal University of Espirito Santo Vitoria, ES, Brazil.
Int J Physiol Pathophysiol Pharmacol. 2012;4(3):167-73. Epub 2012 Sep 20.
BACKGROUND/AIMS: The rat has been the most used experimental animal for studies of cardiovascular and kidney diseases. However, it is notable that there is increasing importance placed on the use of the mouse model to increase understanding of these pathophysiologies. The aim of the present study was to induce chronic kidney disease in a mouse model and to evaluate the resulting changes in blood pressure (BP) and in renal morphology and function.
Adult male C57BL/6 mice underwent 5/6 nephrectomy (5/6 Nx) or a sham operation (Sham). Two weeks later, conscious animals were subjected to a 24-hour urine collection and to a direct measurement of BP.
Compared to Sham animals, 5/6 Nx mice showed reduced creatinine clearance (3-fold, p<0.01), proteinuria (1.5-fold, p<0.01) and uremia (4-fold, p<0.01), as well as high blood pressure (20%, p<0.01). 5/6 Nx animals showed increases in the 24 h urine excretion of Na(+) (2-fold, p<005), K(+) (2-fold, <0.01) and Ca(2+) (12-fold). Kidney histology of 5/6 Nx mice also demonstrated glomerular hypertrophy (1.5-fold, p<0.05), mesangial expansion (40%, p<0.01) and increased glomerular collagen deposition (~30%, p<0.05).
Induction of 5/6 nephrectomy in mice for two weeks leads to systemic arterial hypertension and to functional and morphological damage of the remnant kidney, which are considered the main characteristics of chronic kidney disease.
背景/目的:大鼠一直是心血管和肾脏疾病研究中使用最多的实验动物。然而,值得注意的是,为了增进对这些病理生理学的理解,小鼠模型的使用正变得越来越重要。本研究的目的是在小鼠模型中诱导慢性肾病,并评估由此导致的血压(BP)、肾脏形态和功能的变化。
成年雄性C57BL/6小鼠接受5/6肾切除术(5/6 Nx)或假手术(假手术组)。两周后,对清醒动物进行24小时尿液收集和直接血压测量。
与假手术组动物相比,5/6 Nx小鼠的肌酐清除率降低(3倍,p<0.01)、蛋白尿(1.5倍,p<0.01)和尿毒症(4倍,p<0.01),以及高血压(约20%,p<0.01)。5/6 Nx动物的24小时尿钠(Na+)排泄量增加(2倍,p<0.05)、钾(K+)排泄量增加(约2倍,p<0.01)和钙(Ca2+)排泄量增加(约12倍)。5/6 Nx小鼠的肾脏组织学检查还显示肾小球肥大(1.5倍,p<0.05)、系膜扩张(约40%,p<0.01)和肾小球胶原沉积增加(约30%,p<0.05)。
小鼠5/6肾切除两周可导致系统性动脉高血压以及残余肾脏的功能和形态损伤,这些被认为是慢性肾病的主要特征。