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The Korean Journal of Pathology 2003;37(1): 41-49.
Apoptosis and Cell Proliferation in Experimental Acute Tubular Necrosis Induced by Intramuscular Glycerol Injection.
Wan Seop Kim, Jung Woo Noh, Moon Hyang Park
1Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea. parkmh@hanyang.ac.kr
2Department of Pathology, School of Medicine, Eulji University, Seoul, Korea.
3Department of Internal Medicine, College of Medicine, Hallym University, Seoul, Korea.
BACKGROUND: Acute tubular necrosis (ATN) is the most common cause of acute renal failure. It is characterized by the destruction of tubular epithelial cells. To examine apoptosis and proliferative activity of tubular cells in the course of acute tubular necrosis, we induced acute renal failure by intramuscular hypertonic glycerol injection to New Zealand White rabbits. METHODS: The immunohistochemistry was done for Ki-67 and tissue-transglutaminase (tTG), and the terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) method was performed using a total of 77 renal specimens including 29 gun biopsies and 48 nephrectomiy specimens. RESULTS: Widespread tubular injury with pigment casts and interstitial hemorrhage were noted. The tubular proliferation index was increased at 2 hours after glycerol injection, and the index peaked at 3 hours. The second cell proliferation peak was noted at 3 days. Apoptotic cells were identified by TUNEL and tTG staining. The apoptotic index was significantly increased, and it peaked at 24 hours after glycerol injection. There was a significant correlation between the proliferation index (MIB-1) the and the apototic index (TUNEL)(p= 0.001). A DNA ladder pattern was observed at 6 to 8 hours. CONCLUSIONS: Tubular cell proliferation and apoptosis occur in the early phase after the induction of acute tubular necrosis, and the excess hyperplastic epithelial cells appear to be eliminated by apoptosis.
Key Words: Kidney Tubular Necrosis; Acute; Apotosis; Regeneration
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