Preconditioning effects on expression of proto-oncogenes c-fos and c-jun after hepatic ischemia/reperfusion in rats.
BACKGROUND
Ischemia/reperfusion is the main cause of hepatic damage in liver transplantation. Immediate early genes (IEGs) encode proteins can regulate expression of cellular response genes after injury, and is associated with tissue repair and cell apoptosis. The purpose of this research was to investigate the effects of preconditioning on expression of immediate early genes c-fos and c-jun following hepatic ischemia/reperfusion (IR) and its roles in cellular regeneration and apoptosis.


METHODS
Ninety-six Wistar rats were randomly divided into IR group and hepatic ischemic preconditioning (IPC) group, and each group was further divided into eight sub-groups (n=6). The model of partial liver ischemia/reperfusion was used. The rats were subjected to 60-minute liver ischemia, preceded by 10-minute preconditioning. After 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, 24-hour reperfusion, the serum and liver tissue in each group were collected to detect the level of serum ALT/AST, liver histopathology, expression of c-fos, and c-jun mRNA. Flow cytometer was used to detect Ki67 and Sub-G1 as the quantity indicators of cell regeneration and apoptosis respectively.


RESULTS
Compared with IR group, IPC group showed a significantly lower ALT/AST level in 0.5-hour sub-group to 8-hour sub-group (P<0.05). Ki67 elevated significantly at 0.5, 1, 2 hours, but decreased significantly at 24 hours (P<0.05). Ap index decreased significantly after 1-hour reperfusion (P<0.05). Expressions of c-fos and c-jun mRNA were low, especially c-jun at 0.5, 1 and 2 hours after reperfusion.


CONCLUSIONS
Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, and this protective effect may be related to influence transcription levels of c-fos and c-jun.
Xiao
Jian-Sheng
JS
Research Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. super_xiaoj@163.com
Cai
Fang-Gang
FG
Niu
Ying
Y
Zhang
Yi
Y
Xu
Xian-Ling
XL
Ye
Qi-Fa
QF
D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007511:Ischemia / Q000097:blood* / Q000601:surgery; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply*; D008111:Liver Function Tests; D008297:Male; D008969:Molecular Sequence Data; D011336:Probability; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity
D015415:Biomarkers; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger