Korean J Urol.  2007 Apr;48(4):444-451. 10.4111/kju.2007.48.4.444.

The Histological Changes and Expression of Hypoxia Inducible Factor-1alpha and Vascular Endothelial Growth Factor according to the Differential Renal Function during Total Ureteral Obstruction in the Rabbit Model

• Shim KS
• Lee KM
• Lee SD
• Kim IJ
• Kim JY

• KMID: 1997114
• DOI: http://doi.org/10.4111/kju.2007.48.4.444

Abstract

PURPOSE
The renal histological and hemodynamic changes and the expressions of hypoxia inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) were evaluated according to the differential renal function (DRF) during total ureteral obstruction (TUO) in a rabbit model.
MATERIALS AND METHODS
In forty-nine control (5) and 16 experimental rabbits (16 in TUO 3 days, 13 in TUO 7 days and 15 in TUO 14 days), the renal blood flow (RBF) and 99mTc-DTPA renal scan were measured both before and after TUO. The cut-off of the DRF group was 40%. The histological changes and expressions of HIF-1alpha and VEGF were evaluated using H&E and immunohistochemical stain, respectively.
RESULTS
The entire control group demonstrated more than 40% DRF. Contrary to the control group, the DRF was less than 40% in 4 (25%), 7 (53%) and 6 rabbits (40%) in TUO 3, 7 and 14 day groups, respectively. The postobstructive compared to preobstructive RBF was decreased in each group. The RBF was more decreased in the lower than the higher DRF group (more than 40%) in all of the experimental groups. Abnormal histological changes were more prominent in the experimental groups, and increased with the obstruction time. However, there was no difference in relation to the DRF. The expressions of HIF-1alpha and VEGF were more prominent in the experimental and lower DRF groups.
CONCLUSIONS
During acute TUO, the decreased RBF and hypoxia may play a role in preservation of the DRF.

Keyword

Ureteral obstruction; Kidney function; Hypoxia-inducible factor 1; Vascular endothelial growth factor; Histology

MeSH Terms

Anoxia*
Hemodynamics
Hypoxia-Inducible Factor 1
Rabbits
Renal Circulation
Ureter*
Ureteral Obstruction*
Vascular Endothelial Growth Factor A*
Hypoxia-Inducible Factor 1
Vascular Endothelial Growth Factor A

Figure

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  Fig. 1. Classification of the immunohistochemical staining for hypoxia inducible factor-1 α. (A) Negative (ᅳ), (Β) weak positive (1+), (C) moderate positive (2 +), (D) strong positive (3 +) (x200).

• 

  Fig. 2. Classification of immunohistochemical staining for vascular endothelial growth factor. (A) Negative (—), (B) weak positive (1 +), (C) moderate positive (2 +), (D) strong positive (3 +) (x200).

• 

  Fig. 3. Change in the ipsilateral renal blood flow according to the differential renal function with resect to the duration of the total ureteral obstrucion. (A) Differential renal function >40%, (B) differential renal function <40% (Mann-Whitney test and Wilcox signed rank test; p>0.05). Bar graphs indicate the blood flow of post-obstruction minus that pre-obstruction.

• 

  Fig 4. Hypoxia inducible factor-1 α expressions of ipsilateral kidneys according to the differential renal function with respect to the duration of the total ureteral obstrucion. (A) Differential renal function >40%, (B) differential renal function <40% (Fisher's exact test: p>0.05).

• 

  Fig. 5. Vascular endothelial growth factor expressions of ipsilateral kidneys according to the differential renal function with respect to the duration of the total ureteral obstrucion. (A) Differential renal function>40%, (B) differential renal function<40% (Fisher's exact test: p> 0.05).

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