背景:自发性高血压大鼠(SHR)与年龄相关的血压升高与心脏肥大有关,心力衰竭,和肾损伤。这里,我们首次研究了谷氨酰氨基肽酶(GluAp)的尿酶活性,丙氨酰氨基肽酶(AlaAp),二肽基肽酶-4(DPP4),和Klotho尿液水平,在肾脏中强烈表达的蛋白质,作为SHR肾损伤的早期生物标志物。
方法:研究了2至8月龄的雄性SHR和WistarKyoto(WKY)大鼠。收缩压(SBP),心率(HR),代谢变量,和尿标记物每月测量一次。在研究结束时,对肾脏进行了组织病理学评估.
结果:SHR的肾脏没有出现相关组织病理学改变的迹象,但显示肾小球面积和细胞增加。血浆肌酐下降,研究结束时SHR的肌酐清除率增加。在5个月和8个月大的SHR中,Klotho的尿排泄较高,而血浆Klotho水平与WKY相似。GluAp,AlaAP,在整个时程研究中,SHR和DPP4尿活性增加。观察到肾小球面积和细胞数量与肌酐清除率呈正相关。尿GluAp,AlaAP,DPP4和Klotho与SBP呈正相关。
结论:GluAp,AlaAP,尿液中的DPP4和Klotho是评估早期肾损害的有用工具,在确定肾脏疾病的整个组织病理学和生化表现之前。此外,这些观察结果可能代表了一种新的非侵入性诊断方法,用于评估高血压和其他慢性疾病中肾功能的演变.
BACKGROUND: The age-related increase in blood pressure in spontaneously hypertensive rats (SHRs) is associated to cardiac hypertrophy, heart failure, and renal injury. Here, we investigated for the first time the urinary enzymatic activities of glutamil aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), dipeptidyl peptidase-4 (DPP4), and Klotho urinary levels, proteins that are strongly expressed in the kidney, as early biomarkers of renal injury in SHRs.
METHODS: Male SHR and Wistar Kyoto (WKY) rats were studied from 2 to 8 months old. Systolic blood pressure (SBP), the heart rate (HR), metabolic variables, and urinary markers were measured monthly. At the end of the
study, a histopathological evaluation of the kidney was performed.
RESULTS: Kidneys of SHR did not develop signs of relevant histopathological changes, but showed increased glomerular area and cellularity. Plasma creatinine was decreased, and creatinine clearance was augmented in SHR at the end of the
study. Urinary excretion of Klotho was higher in SHR at 5 and 8 months old, whereas plasma Klotho levels were similar to WKY. GluAp, AlaAp, and DPP4 urinary activities were increased in SHR throughout the time-course
study. A positive correlation between glomerular area and cellularity with creatinine clearance was observed. Urinary GluAp, AlaAp, DPP4, and Klotho showed positive correlations with SBP.
CONCLUSIONS: GluAp, AlaAp, DPP4, and Klotho in the urine are useful tools for the evaluation of renal damage at early stages, before the whole histopathological and biochemical manifestations of renal disease are established. Moreover, these observations may represent a novel and noninvasive diagnostic approach to assess the evolution of kidney function in hypertension and other chronic diseases.