Brandis A, Bianchi G, Reale E, Helmchen U, Kühn K
Lab Invest. 1986 Aug;55(2):234-43.
The development of an age-dependent glomerulosclerosis and proteinuria was investigated in two strains of rats in a model of moderate hypertension comparing rats of the Milan Hypertensive Strain (MHS) with rats of the Milan Normotensive Strain (MNS). Serum creatinine, urinary protein excretion, renal morphology (light- and electronmicroscopy) and morphometry of the media thickness of the intrarenal arteries and of the thickness of the glomerular basement membrane were studied in 2- to 16-month-old MHS and MNS rats. Serum creatinine did not differ between MNS and MHS rats in any age group. MNS rats developed a significant proteinuria which coincided with a glomerulosclerosis in about 22% of the glomeruli at 13 to 16 months. In contrast, urinary protein excretion in MHS rats remained stable during the entire observation period; glomerulosclerosis occurred only in 3% of the glomeruli at 13 to 16 months. As a consequence of hypertension media thickness of intrarenal arteries of MHS rats significantly exceeded that of MNS rats, in the interlobular arteries already at 2 months and in the arcuate arteries at 13 to 16 months. In contrast, thickness of the glomerular basement membrane of MHS rats never exceeded that of MNS rats. From these data we conclude, that glomeruli of MHS rats may be protected against the development of an age-dependent glomerulosclerosis and proteinuria. Further support for this conclusion may also be derived from recent experiments showing that the tubuloglomerular feedback sensitivity is significantly higher in MHS than in MNS rats (41).
在中度高血压模型中，对两种品系的大鼠进行了年龄依赖性肾小球硬化和蛋白尿发展情况的研究，将米兰高血压品系（MHS）大鼠与米兰正常血压品系（MNS）大鼠进行比较。对2至16月龄的MHS和MNS大鼠研究了血清肌酐、尿蛋白排泄、肾脏形态（光镜和电镜）以及肾内动脉中层厚度和肾小球基底膜厚度的形态计量学。各年龄组的MNS和MHS大鼠血清肌酐无差异。MNS大鼠出现明显蛋白尿，在13至16个月时约22%的肾小球出现肾小球硬化。相比之下，MHS大鼠在整个观察期内尿蛋白排泄保持稳定；13至16个月时仅3%的肾小球出现肾小球硬化。由于高血压，MHS大鼠肾内动脉中层厚度显著超过MNS大鼠，在2个月时小叶间动脉就已如此，在13至16个月时弓形动脉也是如此。相比之下，MHS大鼠的肾小球基底膜厚度从未超过MNS大鼠。从这些数据我们得出结论，MHS大鼠的肾小球可能受到保护，不会发生年龄依赖性肾小球硬化和蛋白尿。这一结论的进一步支持也可能来自最近的实验，这些实验表明MHS大鼠的肾小管-肾小球反馈敏感性显著高于MNS大鼠（41）。
