Role of PPARγ in the hematogenous spread of hepatocellular carcinoma after hepatic ischemia reperfusion in mice
10.3760/cma.j.issn.1007-8118.2017.07.013
- VernacularTitle:过氧化物酶体增殖物激活受体γ对小鼠缺血再灌注损伤后肝细胞癌血行转移的影响
- Author:
Yi LIU
;
Zongli ZHANG
;
Runde JIANG
;
Hailin LI
- Keywords:
Hepatocellular carcinoma;
Ischemia/reperfusion;
Peroxisome proliferator-activated receptor γ (PPARγ);
Portal venous metastasis
- From:
Chinese Journal of Hepatobiliary Surgery
2017;23(7):478-482
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of peroxisome proliferator-activated receptor γ (PPARγ) in hematogenous spread of hepatocellular carcinoma after hepatic ischemia reperfusion in mice and its mechanism.Methods One hundred and sixty mice were randomly divided into 4 groups,sham,control,Rosiglitazone(R group) and Rosiglitazone + GW9662 (R + GW).The mice models with hepatic ischemia reperfusion combined with portal vein metastasis of hepatocellular carcinoma were well established.Serum ALT level,expressions of MMP-9,NF-κB and PPARγ,hepatic replacement area (HRA) and survival of mice were compared.Results (1) The median survival in sham group was 16.3 d,R group 12.1 d,control group 9.6 d,R + GW group 8.7 d.(2) Impact on portal venous metastasis:compared with left hepatic lobe (ischemic hepatic lobe) of control group,the HRA was significantly decreased in the left hepatic lobe of sham group (29.1％ vs.13.2％,P ＜0.05).Tumor load was higher in control group than R group (29.1％ vs.13.0％,P ＜ 0.05).(3) Serum ALT level:after 2 h,8 h and 24 h hepatic ischemia reperfusion injury (HIRI),the ALT levels in control group [(1 134.2 ± 320.5) U/L],R group [(1 017.3 ± 365.9)U/L] and R + GW group [(1 344.0 ± 304.3) U/L] were all higher than sham group [(20.6 ± 7.8) U/L],P ＜0.05.With 8 and 24 h HIRI,ALT levels were highest in R + GW group [(4 101.7 ± 462.2) U/L,(3 730.8 ± 582.7) U/L],following by control group [(3 649.1 ± 440.1) U/L,(2 226.7 ± 442.7) U/L],andRgroup [(1691.9±398.6)U/L,(1 109.2±237.4)U/L],P＜0.05.(4) MMP-9 expression:after 8 h HIRI,MMP-9 expression level was predominantly elevated in control group than R group [(41.3 ± 10.7) vs.(4.7 ± 1.1),P ＜ 0.05].Similarly,MMP-9 expression was higher in R + GW group than both control and R groups [(166.9 ± 7.9) vs.(41.3 ± 10.7) and (4.7 ± 1.1),P ＜ 0.05].(5) Expressions of PPARγand NF-κB:in the control group,PPARγ expression emerged after 2 h HIRI,and reached the peak with 8 h HIRI,decreased significantly with 24 h HIRI.NF-κB expression elevated with time,and at the peak with 24 h HIRRI.In R + GW group,the PPARγ expression was similar to control group and high expression of NF-κB were detected at all three endpoints.In R group,marked expression of PPARγ was observed after 2 h HIRI,and reached to peak after 24 h HIRI.NF-κB showed weakly positive expression after 2 h HIRI.Conclusions Rosiglitazone could significantly reduce hematogenous spread of hepatocellular carcinoma after hepatic ischemia reperfusion in mice.This may be attributed to NF-κB expression inhibition by PPARγ up-regulation and decreased MMP-9 production after pretreatment with Rosiglitazone.
