Transient limb ischemia induces remote preconditioning in liver among rats: the protective role of heme oxygenase-1.
BACKGROUND
We have reported the protective role of heme oxygenase-1 (HO-1) in the mechanism of hypoxic preconditioning. We wish to investigate the role of HO-1 in remote preconditioning (RP) against hepatic ischemia/reperfusion (I/R) injury in rats.


METHODS
The remote preconditioning was produced by four cycles of 10-min ischemia-reperfusion of the hind limb of rats. Partial hepatic ischemia was produced in the left lobes for 45 min followed by 240 min of reperfusion. Zinc-protoporphyrin IX (ZnPP), a specific inhibitor of HO enzymatic activity, was intra-peritoneally injected 1 hr before the ischemia-reperfusion injury in separate groups of RP rats. Serum alanine transaminase (ALT) levels, expression of hepatic HO-1 protein and mRNA, immunohistochemical staining and HO enzymatic activity were measured.


RESULTS
HO-1 was induced in the livers of rats 4 hr after the RP stimuli, and the overexpression persisted for 24 hr. Immunohistochemical staining demonstrated induction of HO-1 in the hepatocytes. The peripheral lymphocytes did not express HO-1 after RP. RP diminished the elevation of serum ALT levels 4 hr after I/R injury (283.7+/-167.4 U L) when compared with controls (1297.7+/-729.3 U L) and RP+ ZnPP pretreated groups (1429.9+/-750.9 U L). The heme oxygenase activity in treated rats also correlated these results (286.8+/-34.3 pmol mg protein hr for the RP group, 156.3+/-27.5 pmol mg protein hr for the RP+ ZnPP pretreated group, and 170.6+/-19.4 pmol mg protein hr for the control group, 144.8+/-7.8 pmol mg protein hr for the control+ ZnPP pretreated group).


CONCLUSIONS
Our results indicated that the induction of HO-1 in remote preconditioning played a protective role against hepatic I/R injury.
Lai
I-Rue
IR
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Chang
King-Jen
KJ
Chen
Chau-Fong
CF
Tsai
Hsiu-Wen
HW
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004195:Disease Models, Animal; D005121:Extremities / Q000098:blood supply*; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007511:Ischemia / Q000503:physiopathology*; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D017931:DNA Primers; D051547:Heme Oxygenase-1; D000410:Alanine Transaminase