Expression and role of inducible nitric oxide synthase in ischemia-reperfusion liver in rats.
OBJECTIVE
To investigate the expression and the role of iNOS expression in hepatic ischemia-reperfusion (I/R) injury.


METHODS
Male Wistar rats were subjected to 30-minute hepatic ischemia, then iNOS protein and iNOS mRNA expression in liver tissue was assessed by Western blot and RT-PCR analysis respectively at different time points after reperfusion. The effects of L-NAME (Nomega-nitro-L-arginine methyl ester, a nonselective NOS inhibitor) or AE-ITU (aminoethytl-isothiourea, a relative selective inhibitor of iNOS) treatment were also evaluated.


RESULTS
High levels of iNOS protein and mRNA expression were detected in the liver tissue subjected to I/R, but not in the sham-operated rats. iNOS protein and iNOS mRNA expression reached a maximum on the first day after reperfusion and decreased later. The levels of iNOS protein and iNOS mRNA disappeared on 7th, 3rd day after reperfusion respectively. The high iNOS expression was correlated with hepatic dysfunction. L-NAME administration worsened hepatic dysfunction induced by hepatic I/R. In contrast, AE-ITU  administration showed mild protective effects against hepatic dysfunction induced by hepatic I/R.


CONCLUSIONS
Ischemia-reperfusion may induce or up-regulate the expression of iNOS protein and iNOS mRNA, which is detrimental to hepatic I/R injury
Department of General Surgery and Organ Transplantation Center, Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China. wanglimingjp@yahoo.co.jp
Li-Ming
LM
Wang
Xiao-Feng
XF
Tian
Qian-Ying
QY
Song
Zhen-Ming
ZM
Gao
Fu-Wen
FW
Luo
Chun-Ming
CM
Yang
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008107:Liver Diseases / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C413842:aminoethyl-isothiourea; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D013890:Thiourea; D019331:NG-Nitroarginine Methyl Ester