[The protective effect of heat shock protein 72 by Doxorubicin in cold ischemia-reperfusion injury of the rat liver].
OBJECTIVE
To observe induction of heat shock reaction by pretreatment of Doxorubicin (DXR) in long-term cold preservation-reperfusion injury of the rat liver.


METHODS
The rats were administered intravenously by DXR at a dose of 1 mg/kg body weight in DXR group and by saline in control group. After 48 hours, the rat liver was perfused by using cold University of Wisconsin (UW) solutions and was preserved in UW solution at 4 degrees C for 48 hours. Recipient liver was perfused for 1 and 3 hours after orthotopic liver transplantation. Tumor necrosis factor-alpha (TNF-alpha) mRNA, cytokine-induced neutrophil chemoattractant (CINC) mRNA, macrophage inflammatory protein (MIP-2) mRNA was measured by RT-PCR and heat shock protein 72 (HSP72), nuclear factor-kappaB (NF-kappaB) by Western blot. The serum levels of TNF-alpha, CINC, MIP-2 by ELISA and AST were measured. The survival rate of 7 days was observed.


RESULTS
The expression of TNF-alpha mRNA, CINC mRNA and MIP-2 mRNA was stronger in control group than in DXR group. HSP72 was expressed in SA group but not in control group and oppositely NF-kappaB was expressed in control group but not in DXR group. Serum AST, TNF-alpha, CINC and MIP-2 concentrations were significantly lower in DXR group than in control group (P < 0.05). The survival rate of 7 days was significantly higher in DXR group than in control group (50% vs. 0%, P < 0.05).


CONCLUSIONS
These data suggested that long-term cold ischemia-reperfusion injury was attenuated in liver graft with pretreatment of DXR. The induction of HSP72 may offer protection to hepatocytes by restraining the activation of NF-kappaB and inflammation.
Chen
Hao
H
Center of Organ Transplantation, Ruijin Hospital, Medical School of Shanghai Jiaotong University, Shanghai 200025, China.
Peng
Cheng-hong
CH
Deng
Xia-xing
XX
Qiu
Wei-hua
WH
Shen
Bai-yong
BY
Yang
Wei-ping
WP
Li
Hong-wei
HW
D000818:Animals; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D015925:Cryopreservation; D004317:Doxorubicin / Q000494:pharmacology*; D050884:HSP72 Heat-Shock Proteins / Q000096:biosynthesis*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014022:Tissue Survival; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D019743:Chemokines, CXC; D050884:HSP72 Heat-Shock Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin