Protective effects of HGF-MSP chimer (metron factor-1) on liver ischemia-reperfusion injury in rat model.
OBJECTIVE
It has been reported that metron factor-1 (MF-1), an engineered chimerical factor containing selected functional domains of hepatocyte growth factor and macrophage-stimulating protein (HGF-MSP), could prevent apoptosis and have an anti-inflammatory effect. In this study, we investigate the protective effect of MF-1 on liver ischemia-reperfusion (I/R) injury.


METHODS
Overall 30 Sprague Dawley rats were randomly divided into three groups: the I/R model group (n=12), the MF-1 treatment group (n=12), and the sham-operated group (n=6). Liver I/R injury was induced by clamping the blood supply to the left and median lobes of liver by an atraumatic clamp for 90 min, then removing the clamp and allowing reperfusion. Blood samples were obtained on days 1, 2, 3 and 7 to assess liver biochemistry and the histology of liver tissue. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), endothelial nitric oxide synthase and inducible nitric oxide synthase were measured. In addition, the anti-oxidative effect of MF-1 on hepatocytes was assessed in vitro.


RESULTS
MF-1 treatment improved the rat survival rate significantly (P < 0.05). Liver biochemistry and histological changes were significantly ameliorated. MDA increased and SOD and NO decreased in the liver tissue. In vitro, MF-1 protected the human hepatic cell line HL-7702 from damage of oxidative stress.


CONCLUSIONS
MF-1 could protect the liver from I/R injury, which might involve the reduction of oxygen free radicals and the increase of NO synthesis in an injured liver.
Xue
Feng
F
Organ Transplantation Center, Renji Hospital, Shanghai Jiaotong University School of Medicine, China. fengxue6879@yahoo.com.cn
Zhang
Jian Jun
JJ
Xu
Long Mei
LM
Zhang
Cheng
C
Xia
Qiang
Q
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D016207:Cytokines / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D015996:Survival Rate
D000975:Antioxidants; D016207:Cytokines; D011993:Recombinant Fusion Proteins; C529731:metron factor-1; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase