Compensatory hepatic regeneration after mild, but not fulminant, intraperitoneal sepsis in rats
| Autor: | Lisa Bellin, Patrick K. Kim, Kenneth M. Andrejko, Nichelle Raj, Emma E. Furth, Charlotte A Haaxma, Yoram Weiss, Clifford S. Deutschman |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Necrosis Transcription Genetic Proto-Oncogene Proteins c-jun Physiology Fulminant Apoptosis Biology Rats Sprague-Dawley Sepsis Cecum Physiology (medical) In Situ Nick-End Labeling medicine Animals Cyclin D1 RNA Messenger Interleukin 6 Glutathione Transferase Cause of death Activating Transcription Factor 3 Hepatology Gastroenterology medicine.disease Liver regeneration Liver Regeneration Rats Surgery DNA-Binding Proteins medicine.anatomical_structure Liver Anesthesia biology.protein Tumor necrosis factor alpha medicine.symptom Biomarkers |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 280:G968-G973 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.2001.280.5.g968 |
| Popis: | Sepsis is the leading cause of death in surgical intensive care units. Although both mild sepsis secondary to cecal ligation and single puncture (CLP) and fulminant, double puncture CLP (2CLP) may provoke hepatocyte death, we hypothesize that regeneration compensates for cell death after CLP but not 2CLP. In male Sprague-Dawley rats, hepatic necrosis, as determined by serum α-glutathione S-transferase (α-GST) levels, was significantly but equally elevated over time after both CLP and 2CLP. Apoptosis, evaluated using both terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and morphological examination, was minimal after both CLP and 2CLP. Regeneration, assayed by staining tissue for incorporation of exogenously administered bromodeoxyuridine, was present after CLP but not after 2CLP. To further substantiate impaired regeneration, steady-state levels of mRNAs encoding JunB, LRF-1, and cyclin D1 were determined. After 2CLP, the absence of JunB, LRF-1, and cyclin D1 mRNAs confirmed failed activation of the mitogen-activated protein kinase-linked proliferative pathway and progression through the cell cycle. Therefore, failed hepatocyte regeneration may be a manifestation of hepatic dysfunction in fulminant sepsis. |
| Databáze: | OpenAIRE |
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