米兰正常血压品系中糖尿病肾病的发展，而米兰高血压品系中则不然：血流动力学可能起允许作用。

Development of diabetic nephropathy in the Milan normotensive strain, but not in the Milan hypertensive strain: possible permissive role of hemodynamics.

作者信息

Pugliese Giuseppe, Pricci Flavia, Barsotti Paola, Iacobini Carla, Ricci Carlo, Oddi Giovanna, Romeo Giulio, Leto Gaetano, Marano Giuseppe, Sorcini Mariella, Sabbatini Massimo, Fuiano Giorgio, Di Mario Umberto, Pugliese Francesco

机构信息

Department of Clinical Sciences and Department of Experimental Medicine and Pathology, "La Sapienza" University, Rome, Italy.

出版信息

Kidney Int. 2005 Apr;67(4):1440-52. doi: 10.1111/j.1523-1755.2005.00221.x.

DOI:10.1111/j.1523-1755.2005.00221.x

PMID:15780096

Abstract

BACKGROUND

Rats of the Milan normotensive strain develop spontaneous glomerulosclerosis, whereas those of the Milan hypertensive strain are resistant to renal disease, possibly due to intrarenal artery hypertrophy protecting from systemic hypertension. To assess the role of hemodynamic versus metabolic factors in diabetic nephropathy, we investigated whether streptozotocin-induced diabetes accelerates glomerulosclerosis in Milan normotensive and/or removes (the hemodynamic) protection in Milan hypertensive rats by reducing preglomerular vascular resistance.

METHODS

Diabetic and nondiabetic Milan normotensive, hypertensive, and progenitor Wistar rats were followed for 6 months for the assessment of renal function and structure.

RESULTS

Proteinuria increased in nondiabetic and diabetic normotensive and, to a lesser extent, in diabetic Wistar, but not hypertensive rats. Serum creatinine increased and creatinine clearance decreased in nondiabetic and diabetic normotensive rats at 6 months. At 1.5 months, diabetic normotensive, but not hypertensive rats showed increased glomerular filtration rate and filtration fraction, suggesting glomerular hypertension. Diabetic nephropathy was detected in diabetic normotensive and Wistar, but not hypertensive rats. Glomerular extracellular matrix and TGF-beta mRNA levels increased with diabetes (and age) in normotensive, but not hypertensive rats. Arterioles and interlobular arteries showed increased media thickness in hypertensive versus normotensive rats, with diabetes reducing it only in the normotensive.

CONCLUSION

These data show that Milan hypertensive rats are not susceptible to diabetic nephropathy, at variance with glomerulosclerosis-prone Milan normotensive rats, thus indicating the importance of genetic background. Our study suggests that the nature of this (genetic) protection might be hemodynamic, with intrarenal artery hypertrophy preventing diabetes-induced loss of autoregulation.

摘要

背景

米兰正常血压品系的大鼠会发生自发性肾小球硬化，而米兰高血压品系的大鼠对肾脏疾病具有抗性，这可能是由于肾内动脉肥大可抵御系统性高血压。为了评估血流动力学因素与代谢因素在糖尿病肾病中的作用，我们研究了链脲佐菌素诱导的糖尿病是否会加速米兰正常血压大鼠的肾小球硬化，以及/或者通过降低肾小球前血管阻力消除（血流动力学方面的）对米兰高血压大鼠的保护作用。

方法

对糖尿病和非糖尿病的米兰正常血压大鼠、高血压大鼠以及祖系Wistar大鼠进行6个月的跟踪观察，以评估其肾功能和结构。

结果

非糖尿病和糖尿病正常血压大鼠以及程度较轻的糖尿病Wistar大鼠蛋白尿增加，但高血压大鼠未出现。6个月时，非糖尿病和糖尿病正常血压大鼠血清肌酐升高，肌酐清除率降低。1.5个月时，糖尿病正常血压大鼠而非高血压大鼠肾小球滤过率和滤过分数增加，提示存在肾小球高血压。糖尿病肾病在糖尿病正常血压大鼠和Wistar大鼠中被检测到，但高血压大鼠未出现。正常血压大鼠而非高血压大鼠中，糖尿病（和年龄增长）会使肾小球细胞外基质和转化生长因子-β mRNA水平升高。与正常血压大鼠相比，高血压大鼠的小动脉和小叶间动脉中膜厚度增加，糖尿病仅使正常血压大鼠的中膜厚度降低。