Glycine blunts transplantative liver ischemia-reperfusion injury by downregulating interleukin 1 receptor associated kinase-4

• Published in: Acta pharmacologica Sinica Vol. 27; no. 11; pp. 1479 - 1486
• Main Authors: Liu, Zuo-jin, Yan, Lu-nan, Li, Shen-wei, You, Hai-bo, Gong, Jian-ping
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.11.2006
• Subjects: Animals; Down-Regulation; Glycine - pharmacology; Interleukin-1 Receptor-Associated Kinases - biosynthesis; Interleukin-1 Receptor-Associated Kinases - genetics; Lipopolysaccharides - blood; Liver - pathology; Liver - ultrastructure; Liver Transplantation - adverse effects; Male; NF-kappa B - metabolism; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury - etiology; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Tumor Necrosis Factor-alpha - metabolism; 氨基乙酸; 白细胞介素; 缺血再灌注损伤; 肝疾病
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2006.00413.x

Aim： To determine whether glycine could downregulate interleukin 1 receptor associated kinase-4 （IRAK-4） expression to interfere with lipopolysaccharides （LPS） signal transduction and blunt transplantative liver ischemia-reperfusion injury （I/RI）. Methods： SD rats were randomly divided into two groups： donor animals of the glycine group （n=40） were given glycine （1.5 mL; 300 mmol/L, iv） 1 h before harvest, and the control group were treated with 1.5 mL physiological saline （n= 40）. Orthotropic liver transplantation was then performed according to the Kamada technique. Ten animals in each group were followed up for 7 d after surgery to assess survival. The remaining animals in each group were divided into 3 subgroups （n=10） at lh, 2 h and 6 h after portal vein reperfusion. Levels of LPS, serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT） and total bilirubin in portal circulation, as well as IRAK-4 and TNF-α expression, NF-κB transcriptional activity and morphological study of liver tissues were analyzed. Results： Reperfusion resulted in a significant elevation of LPS concentrations in each group persisting to the end of our study. However, glycine, which led to improved survival rate and liver function, significantly alleviated liver parenchyma cell damage by downregulating IRAK-4, TNF-α expression and NF-κB transcriptional activity compared with the control group. Conclusion： Glycine can attenuate hepatic I/RI by downregulating IRAK-4 to interfere with LPS signal transduction.