Ki Sik Shim; Kyung Mi Lee; Sang Don Lee; In Joo Kim; Ji Yeon Kim

doi:10.4111/kju.2007.48.4.444

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Shim, Lee, Lee, Kim, and Kim: The Histological Changes and Expression of Hypoxia Inducible Factor-1α and Vascular Endothelial Growth Factor according to the Differential Renal Function during Total Ureteral Obstruction in the Rabbit Model

Original Article

Korean J Urol 2007;48(4):444-451.

Published online: 18 December 2007

DOI: https://doi.org/10.4111/kju.2007.48.4.444

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

Ki Sik Shim¹, Kyung Mi Lee^2,⁵, Sang Don Lee^2,^5,, In Joo Kim^3,⁵, Ji Yeon Kim^4,⁵

¹From the Department of Urology College of Med- cine, Pusan National University, Busan, Korea

²Departments of Veterans Hospital College of Med- cine, Pusan National University, Busan, Korea

³Departments of Urology, Nuclear Medcine College of Med- cine, Pusan National University, Busan, Korea

⁴Departments of Pathology College of Med- cine, Pusan National University, Busan, Korea

⁵Departments of Medcal Research Institute, College of Med- cine, Pusan National University, Busan, Korea

Corresponding Author: Lee Sang-don Department of Urology, Pusan National University Hospital 1-ga, Ami-dong, Seo-gu, Busan 10 street 602-730 TEL: 051-240-7348 FAX: 051-247-5443 E-mail: lsd@pusan.ac.kr

Received 11 October 2006 Accepted 6 March 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose:

lurpHIB The renal histological and hemodynamic changes and the expressions of hypoxia inducible factor-1 α (HIF-1 α) 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:

MMHMIs βλ MUklflfeB 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-1 α and VEGF were evaluated using H&E and immunohistochemical stain, respectively.

Results:

RHuUlB 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-1 α 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.

Keywords: Ureteral obstruction, Kidney function, Hypoxia-inducible factor 1, Vascular endothelial growth factor, Histology

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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).

Table 1.

Microscopic findings of ipsilateral kidneys according to the duration of the total ureteral obstruction and differential renal function

Group		No. of glomerulus	Dilatation of Bowman's space	Dilatation of collecting duct^†	Dilatation of proximal tubule†	Interstitial fibrosis †	Interstitial inflammation^†
Control		58 ±13.0	0	0.6 ±0.9	0	0	0.6 ±0.8
Postop.	A	49.8 ±16.4	0.5 ±0.5	1.1 ±0.7	0.6 ±0.5	0	0.3 ±0.4
3 days	B	45.0 ±5.7	0.5 ±0.5	1.25 ±0.5	0.5 ±0.5	0.25 ±0.5	0.25 ±0.5
Postop.	A	46.0±11.1	0.7±1.1	1.7±0.7	0.9 ±0.3	0.1 ±0.3	0.7 ±0.7
7 days	B	52.3 ±12.0	0.8 ±0.4	1.3±0.8	0.8 ±0.4	0.2 ±0.4	0.5 ±0.5
Postop.	A	48.3±11.6	0.3 ±0.5	1.8 ±0.4	1.3 ±0.5	0.7 ±0.5	1.2 ±0.7
14 days	B	43.0 ±10.8	0.2 ±0.4	1.6 ±0.5	1.0 ±0.6	1.2 ±0.7	1.8 ±0.4

∗: focal segmental glomerulous sclerosis. A: differential renal function >40%, B: differential renal function <40%. Statistical analysis by Mann Whitney test and Kruskal Wallis test († p < 0.05)

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