Protective Effects of Erythropoietin on Endotoxin-related Organ Injury in Rats

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 33; no. 5; pp. 680 - 686
• Main Author: 李秀江 张国兴 孙霓 孙字 杨立志 杜玉君
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2013; Intensive Care Unit, Tumor Hospital of Jilin Province, Changchun 130012, China%Department of Nephrology, First Hospital of Jilin University, Changchun 130021, China
• Subjects: Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; Blood Urea Nitrogen; Blotting, Western; Creatinine - blood; Endotoxins; Erythropoietin - administration & dosage; Erythropoietin - genetics; Erythropoietin - pharmacology; Injections, Intravenous; Kidney - drug effects; Kidney - metabolism; Kidney - ultrastructure; Lipopolysaccharides; Liver - drug effects; Liver - metabolism; Liver - ultrastructure; Lung - drug effects; Lung - metabolism; Lung - ultrastructure; Male; Medicine; Medicine & Public Health; Microscopy, Electron, Transmission; Multiple Organ Failure - blood; Multiple Organ Failure - chemically induced; Multiple Organ Failure - prevention & control; NF-kappa B - metabolism; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Tumor Necrosis Factor-alpha - blood; 丙氨酸转氨酶; 保护作用; 内毒素; 器官功能; 大鼠模型; 组织学检查; 缺血再灌注损伤; 重组人促红细胞生成素; lipopolysaccharide; multiple organ injury; erythropoietin
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-013-1180-1

Summary： The protective effect of erythropoietin （EPO） on tissues following ischemia and reperfusion injuries remains poorly understood. We aimed to investigate the effect of EPO in preventing en- dotoxin-induced organ damage. Rat model of multiple organ failure （MOF） was established by tail vein injection of 10 mg/kg lipopolysaccharide （LPS）. Recombinant human EPO treatment （5000 U/kg） was administered by tail vein injection at 30 min after LPS challenge. Twenty-four h after EPO treatment, changes in serum enzyme levels, including aspartate aminotransferase （AST）, alanine transaminase （ALT）, blood urea nitrogen （BUN） and creatinine （Cr）, were evaluated by biochemical analysis. Serum levels of tumor necrosis factor-tx （TNF-ct） were determined by using immunoradiometric assay. Histological examination of tissue sections was carried out by hematoxylin and eosin staining, while ul- trastructure evaluation of organ tissues was assessed by transmission electron microscopy. Protein ex- pression levels were detected by using Western blotting. EPO treatment showed a modest effect in pre- venting LPS-induced elevation of AST, ALT, BUN, Cr, and TNF-ct levels, and in protecting against LPS-induced tissue degeneration and injured ultrastructure in the lung, liver, and kidney. Moreover, LPS promoted phosphorylation of alanine aminotransferase （AKT） and increased nuclear factor-r,B （NF-rB） activation in the lung, liver, and kidney （P〈0.05 vs. control）. However, EPO treatment significantly de- creased the LPS-induced pAKT up-regulation in these tissues （P〈0.05 vs. LPS treatment alone）. The present study demonstrates that EPO may play a protective role against LPS-induced MOF by reducing the inflammatory response and tissue degeneration, possibly via the phosphatidylinositol 3-kinase/AKT and NF-r,B signaling pathways.