Renal fibrosis in diabetic and aortic-constricted hypertensive rats
Renal fibrosis in diabetic and aortic-constricted hypertensive rats
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DOI：
10.1152/ajpregu.2001.280.6.r1823
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发表时间：
2001-06-01
影响因子：
2.8
通讯作者：
Pérez-Barriocanal, F
中科院分区：
文献类型：
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作者：
Gallego, B;Arévalo, MA;Pérez-Barriocanal, F
为了评估在糖尿病和高血压大鼠中观察到的肾损害是否是由于血液动力学或代谢变化，在链脲佐菌素诱导的糖尿病大鼠（收缩1糖尿病组）和非糖尿病大鼠（收缩组）中进行了两个肾动脉之间的进行性主动脉收缩。该模型允许我们研究在相同代谢环境中受到不同灌注压（PP）的两个肾脏。对一个月大的大鼠（100-120 g体重）进行主动脉缩窄手术。缩窄后3个月，两组的肾小球滤过率和肾血浆流量相似。放置在结扎线上方的肾脏[收缩高压肾脏（CH）或收缩1糖尿病高压肾脏（DH）]中的PP大于放置在结扎线下方的肾脏[收缩低压（CL）或收缩1糖尿病低压（DL）]。CH肾的蛋白尿高于CL肾（分别为512 ± 61和361 ± 38 mug/30 min），DH肾的蛋白尿更高（770 ± 106 mug/30 min）。使用计算机辅助图像分析系统在用叙利亚红染色的组织切片中测量肾纤维化。DH和DL肾脏的红细胞截面积和毛细血管簇面积均高于CH和CL肾脏。DH肾表现出轻微的系膜扩张和毛细血管壁增厚，前者更为明显。CH组和DH组的大多数肾小体在形态上几乎正常，仅在某些情况下观察到系膜的轻微增加。转化生长因子-β 1（TGF-β 1）的免疫组化显示，DH肾表现出最高的肾小球表达。我们的结论是：1）糖尿病动物发生肾小球纤维化而非间质纤维化的程度高于非糖尿病动物，并且这种病变主要发生在高血压肾（DH），2）TGF-β表达增加与糖尿病肾损伤相关。
To assess if the renal damage observed in rats with diabetes and hypertension is due to hemodynamic or metabolic changes, a progressive aortic constriction between the two renal arteries has been done in streptozotocin-induced diabetic rats (constriction 1 diabetes group) and in nondiabetic rats (constriction group). This model allows us to study two kidneys subjected to different perfusion pressure (PP) in the same metabolic environment. One-month-old rats (100-120 g body wt) were subjected to the aortic constriction procedure. Three months after constriction, glomerular filtration rate and renal plasma flow were similar in both kidneys of the two groups. PP was greater in the kidney placed over the ligature [constriction high-pressure kidney (CH) or constriction 1 diabetic high-pressure kidney (DH)] than in the one placed below the ligature [constriction low pressure (CL) or constriction 1 diabetic low pressure (DL)]. Proteinuria was higher in the CH than in the CL kidneys (512 +/- 61 vs. 361 +/- 38 mug/30 min, respectively) and much higher in the DH kidney (770 +/- 106 mug/30 min). Renal fibrosis was measured in tissue sections stained with Syrius red using a computer-assisted image analysis system. DH and DL kidneys showed higher corpuscular cross-sectional and capillary tuft areas than the CH and CL ones. The DH kidney showed slight mesangial expansion and thickening of the capillary walls, which were more pronounced in the former. Most renal corpuscles from CH and DH groups were nearly normal in morphology appearance, and only in some instances a slight increment in mesangium was observed. Transforming growth factor-beta1 (TGF-beta1) immunostaining revealed that DH kidneys showed the highest glomerular expression. We concluded that 1) diabetic animals develop glomerular but not interstitial fibrosis to a greater extent than nondiabetic animals and that this lesion principally occurs in the hypertensive kidney (DH), and 2) increased TGF-beta expression is associated with diabetic renal damage.