The Serial Microscopic Changes of Cell Proliferative and Apoptotic Phenomenon in Obstructed Ureters in the Rat

Kim, Hyeong Gon; Kwak, Chul; Kim, Hyun Hoe; Paick, Sung Hyun; Lho, Yong Soo; Lee, Jong Wook; Jo, Moon Ki

Abstract

Purpose
Obstructive uropathy due to a ureteral obstruction is one of the most common diseases of the urinary tract, and can lead to severe renal injury and ureteral damage. This study performed to elucidate the histological findings and serial changes in the apoptotic and proliferative phenomena in the pathogenesis of ureteral damage during the course of obstructive uropathy in ligated rat ureters.
Materials and Methods
After unilateral ligation of the ureter, each group of five Sprague-Dawley rats was sacrificed, and examined 1, 5, 10, 15, 20, 25, 30 and 35 days after ligation: five rats with normal ureters were also examined as controls. The cell proliferation and apoptosis were detected with proliferating cell nuclear antigen (PCNA) immunohistochemistry and a terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) in situ nick-end labeling (TUNEL) study, respectively, in 45 Sprague-Dawley rats.
Results
The epithelial layer was thickened in the 5 day-obstructed ureters (DOUs). The severity of thickening of the fibrous and smooth muscle layers progressed consistently to the 15 DOUs, which was maintained until day 35. The expression of PCNA in the epithelial layer was present in every ureter, with a significant increase of labeled cells in the 1 and 5 DOUs. The expressions of PCNA in the fibrous and smooth muscle layers were present from day 10 after ligation and maintained until day 20, but then significantly declined at 25 DOUs. TUNEL-positive cells were shown in the epithelial layer in the 10, 15, 20, 25, 30 and 35 DOUs. The mean numbers of TUNEL-positive cells in the 20, 25 and 30 DOUs were significantly higher than those in the 10 DOUs, and reached their peak in the 25 DOUs. Positive cells were shown in the fibrous and smooth muscle layers in the 25, 30 and 35 DOUs.
Conclusions
Apoptosis and cell proliferation may play an important role in the pathogenesis of ureteral damage in obstructed ureters. The peak of apoptosis was shown in the 25 DOUs.