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

作　　者：Zuo-jin LIE Lu-nan YAN Shen-wei LI Hai-bo YOU Jian-ping GONG 

机构地区：[1]Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400010, China [2]Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China

出　　处：《Acta Pharmacologica Sinica》2006年第11期1479-1486,共8页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China(№30471696,30500473);the PhD Programs Foundation of Ministry of Education of China(№20050631001);the Natural Science Foundation of Chongqing(№2005BB5242).

摘　　要：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.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.

关 键 词：liver transplantation reperfusion injury GLYCINE LIPOPOLYSACCHARIDES IRAK-4 

分 类 号：R575[医药卫生—消化系统]