Koike T, Tomoda F, Kinuno H, Inoue H, Takata M
The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan.
Acta Physiol Scand. 2005 May;184(1):73-81. doi: 10.1111/j.1365-201X.2005.01418.x.
The aim of this study was to investigate the renal structural properties in diabetic nephropathy.
Flow-pressure and pressure-glomerular filtration rate (GFR) relationships were determined for maximally vasodilated kidneys at 10 (pre-diabetic stage) and 42 weeks of age (diabetic stage) in Otsuka Long-Evans Tokushima Fatty rats (OLETF), an animal model of type 2 diabetes mellitus, using age-matched Long-Evans Tokushima Otsuka rats (LETO) as non-diabetic controls (n = 9 of each age for each strain). Kidneys were then perfusion-fixed for histological analysis.
At 10 weeks of age, the slope of flow-pressure relationship (minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature) was steeper in OLETF than in LETO. In contrast, the threshold pressure for beginning filtration (preglomerular-to-postglomerular vascular resistance ratio) at pressure-GFR relationship did not differ between the two strains; however, the slope of the relationship (glomerular filtration capacity) was lower in OLETF than in LETO. Thus, in the kidneys of 10-week-old OLETF rats, vascular narrowing and impaired glomerular filtration capacity already existed with no abnormalities in preglomerular-to-postglomerular vascular resistance ratio. From the age of 10-42 weeks, the following results were obtained: (1) Minimal renal vascular resistance decreased in both strains, but it diminished markedly in OLETF. (2) The pressure for beginning filtration increased in LETO, but remained unchanged in OLETF. (3) Glomerular filtration capacity decreased to the similar extent in both strains. (4) Histologically, the vascular lumen and wall thickness increased in the interlobular arteries of both strains. However, vascular luminal widening was more pronounced in OLETF, resulting in the reduction in wall to lumen ratio. (5) Glomerular injuries and increased blood pressure occurred only in OLETF.
In conclusion, during progression from the prediabetic to diabetic stage of OLETF, the pre-existing vascular narrowing was markedly attenuated without the concomitant increase in preglomerular-to-postglomerular vascular resistance ratio. Combined with increased blood pressure, these renal structural alterations could lead to the elevation of intraglomerular pressure in OLETF.
本研究旨在调查糖尿病肾病中的肾脏结构特性。
使用年龄匹配的大耳白兔（LETO）作为非糖尿病对照（每个品系各年龄组均为n = 9），测定2型糖尿病动物模型大耳白兔（OLETF）在10周龄（糖尿病前期）和42周龄（糖尿病期）时最大血管扩张状态下肾脏的血流-压力和压力-肾小球滤过率（GFR）关系。然后对肾脏进行灌注固定以进行组织学分析。
10周龄时，OLETF中血流-压力关系的斜率（最小肾血管阻力，反映肾小球前和肾小球后血管系统的总体管腔尺寸）比LETO更陡。相比之下，压力-GFR关系中开始滤过的阈值压力（肾小球前与肾小球后血管阻力比）在两个品系之间没有差异；然而，OLETF中该关系的斜率（肾小球滤过能力）低于LETO。因此，在10周龄的OLETF大鼠肾脏中，血管狭窄和肾小球滤过能力受损已经存在，而肾小球前与肾小球后血管阻力比没有异常。从10 - 42周龄，获得以下结果：（1）两个品系的最小肾血管阻力均降低，但OLETF中显著降低。（2）LETO中开始滤过的压力升高，而OLETF中保持不变。（3）两个品系的肾小球滤过能力下降程度相似。（4）组织学上，两个品系的小叶间动脉血管腔和壁厚度均增加。然而，OLETF中血管腔扩张更明显，导致壁腔比降低。（5）仅在OLETF中出现肾小球损伤和血压升高。
总之，在OLETF从糖尿病前期进展到糖尿病期的过程中，先前存在的血管狭窄明显减轻，而肾小球前与肾小球后血管阻力比没有相应增加。结合血压升高，这些肾脏结构改变可能导致OLETF中肾小球内压力升高。
