Renal Research Group, Institute of Medicine, University of Bergen, Bergen, Norway.
J Hypertens. 2013 Jan;31(1):152-9. doi: 10.1097/HJH.0b013e32835a5d4e.
The progression of damage in the renal cortex has not been investigated in the nonclipped kidney of the two-kidney, one-clip model of renal hypertension. In other hypertensive models, damage has been found to progress from the juxtamedullary cortex (JMC) and outward, which has been attributed to early vascular effects.
The present study investigated the relation between perivascular deposition of collagen and structural damage after 16 and 24 weeks of hypertension in the nonclipped kidney in rats.
Periarterial collagen density in the kidney was significantly increased already 16 weeks after clipping, at that time tubulointerstitial damage was not evident. After 24 weeks of clipping, periarterial collagen was further increased, and tubulointerstitial damage had developed in the JMC, whereas the outer cortex was protected. Interstitial collagen was not significantly increased in any cortex part during the course of the experiment. Collagen type I a1 mRNA was increased in the JMC after 24 weeks, and α smooth muscle actin histochemistry and collagen type I a2 in-situ hybridization identified myofibroblasts around the arteries after 16 and 24 weeks as the major source of this increase.
Fibrosis in the nonclipped kidney of renal hypertensive rats starts around the juxtamedullary resistance vessels and then progresses in the JMC, whereas the outer cortex is protected. This suggests that pressure-induced injury to the vasculature attracts or activates fibroblasts in the perivascular area, which may allow damage to progress by impairing vessel function.
在两肾一夹型肾高血压模型中，尚未对未夹闭肾脏的肾皮质损伤进展进行研究。在其他高血压模型中，已发现损伤从肾髓质旁皮质（JMC）向外进展，这归因于早期血管效应。
本研究在大鼠中调查了高血压 16 和 24 周后，血管周围胶原沉积与非夹闭肾脏结构损伤之间的关系。
夹闭后 16 周，肾血管周围胶原密度显著增加，此时肾小管间质损伤不明显。夹闭 24 周后，血管周围胶原进一步增加，JMC 出现肾小管间质损伤，而外皮质则得到保护。在实验过程中，任何皮质部分的间质胶原均无明显增加。24 周后 JMC 中 I 型胶原 a1 mRNA 增加，α平滑肌肌动蛋白组织化学和 I 型胶原 a2 原位杂交鉴定出 16 和 24 周后动脉周围的肌成纤维细胞是这种增加的主要来源。
肾高血压大鼠未夹闭肾脏的纤维化始于肾髓质旁阻力血管周围，然后在 JMC 中进展，而外皮质则得到保护。这表明血管损伤导致血管周围区域的成纤维细胞被吸引或激活，从而可能通过损害血管功能导致损伤进展。
