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Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats

World Journal of Hepatology 2014年第2期6卷 72-84页

作者： Tomohide Hori Shinji Uemoto Feng Chen Lindsay B Gardner Ann-Marie T Baine Toshiyuki Hata Takayuki Kogure Justin H Nguyen Division of Hepato-Biliary-Pancreatic and Transplant Surgery Department of Surgery Kyoto University Graduate School of Medicine Department of Neuroscience Mayo Clinic Department of Gastroenterology Tohoku University Graduate School of Medicine Division of Transplant Surgery Department of Transplantation Mayo Clinic

AIM:To investigate oxidative stress(OS)-mediated damage and the behavior of extracellular matrices in various rat models because shear stress with portal hypertension and cold ischemia/warm reperfusion injury trigger the liver regeneration cascade after surgery. These injuries also cause fatal liver ***: Rats were divided into four groups according to the surgery performed: control; hepatectomy with 40% liver remnant(60% hepatectomy); orthotopic liver transplantation(OLT) with whole liver graft(100% OLT); and split OLT(SOLT) with 40% graft(40% SOLT). Survival was evaluated. Blood and liver samples were collected at 6 h after surgery. Biochemical and histopathological examinations were performed. OSinduced damage, 4-hydroxynonenal, ataxia-telangiectasia mutated kinase, histone H2AX, phosphatidylinositol 3-kinase(PI3K) and Akt were evaluated by western blotting. Behavior of extracellular matrices, matrix metalloproteinase(MMP)-9, MMP-2, tissue inhibitor of metalloproteinase(TIMP)-1 and TIMP-2 were also evaluated by western blotting and zymography. RESULTS: Although 100% OLT survived, 60% hepatectomy and 40% SOLT showed poor survival. Histopathological, immunohistological, biochemical and protein assays revealed that 60% hepatectomy, 100% OLT and 40% SOLT showed liver damage. PI3K and Akt were decreased in 60% hepatectomy and 40% SOLT. For protein expression, 40% SOLT showed differences in MMP-9, MMP-2 and TIMP-2. TIMP-1 showed differences in 60% hepatectomy and 40% SOLT. For protein activity, MMP-9 demonstrated significant differences in 60% hepatectomy, 100% OLT and 40% SOLT. CONCLUSION: Under conditions with an insufficient liver remnant, prevention of OS-induced damage via the Akt/PI3K pathway may be key to improve the postoperative course. MMP-9 may be also a therapeutic target after surgery.

关键词： Free radicals Akt Phosphatidylinositol 3-ki-nase Matrix metalloproteinase Tissue inhibitors of metalloproteinase

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