Expression of iNOS in early injury in a rat model of small-for-size liver transplantation.
BACKGROUND
Living donor liver transplantation has been widely accepted as the treatment of choice for end-stage liver disease. Large amounts of nitric oxide generated by inducible nitric oxide synthase (iNOS) have been shown to play an important role in many inflammatory and immune reactions, but expression of iNOS in small-for-size liver transplantation is unknown. The aims of this study were to determine the time course of iNOS mRNA and protein as well as the redox state of liver biopsies in a rat model of small-for-size liver transplantation.


METHODS
Male Sprague-Dawley rats were divided into a control group, a warm ischemia-reperfusion (IR) group, and a small-for-size liver graft group. Real-time RT-PCR and Western blotting were used to characterize the time course of the expression of iNOS mRNA and protein, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) were used as markers to characterize the redox state of liver tissues, and the time courses of MDA and SOD levels were also measured.


RESULTS
The expression of iNOS mRNA and protein levels in the warm IR and small-for-size graft groups both significantly increased after reperfusion, and peaked at 3 hours. Moreover, the increase in MDA was accompanied by increased iNOS in the period of 1-24 hours after reperfusion. The MDA levels in the warm IR and small-for-size graft groups significantly increased after reperfusion, peaked at 3 hours, and decreased thereafter. The direction of change in SOD was opposite that of the change in MDA.


CONCLUSIONS
The expression of iNOS mRNA and protein is activated after reperfusion both in hepatic warm IR injury and small-for-size liver graft. Furthermore, the results of this study suggest that iNOS contributes to the damage in warm IR injury and small-for-size grafts via free oxygen radicals.
The National Institute of Living Donor Liver Transplantation, Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Wei-Wei
WW
Jiang
Lian-Bao
LB
Kong
Guo-Qiang
GQ
Li
Xue-Hao
XH
Wang
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D005609:Free Radicals; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology
D005609:Free Radicals; D012333:RNA, Messenger; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase