SOD Mimetic Improves the Function, Growth, and Survival of Small-Size Liver Grafts After Transplantation in Rats

被引:12
作者
Cui, Yi-Yao [1 ,2 ]
Qian, Jian-Min [3 ]
Yao, Ai-Hua [1 ]
Ma, Zhen-Yu [3 ]
Qian, Xiao-Feng [1 ]
Zha, Xiao-Min [1 ]
Zhao, Yi [1 ]
Ding, Qiang [1 ]
Zhao, Jia [1 ]
Wang, Shui [1 ]
Wu, Jian [2 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Gen Surg, Nanjing 210029, Jiangsu, Peoples R China
[2] Univ Calif Davis, Med Ctr, Dept Internal Med, Div Gastroenterol & Hepatol, Sacramento, CA 95817 USA
[3] Fudan Univ, Huashan Hosp, Ctr Organ Transplantat, Liver Transplant Sect, Shanghai 200433, Peoples R China
基金
美国国家卫生研究院;
关键词
Living-donor liver transplantation; Small-for-size syndrome; Oxidant stress; SOD mimetics; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; PROTEIN-KINASE; GENE DELIVERY; INJURY; MICE; REGENERATION; HEPATOCYTES; ANTIOXIDANT; MODEL;
D O I
10.1097/TP.0b013e3182633478
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Background. Small-for-size syndrome (SFSS) may occur when graft volume is less than 45% of the standard liver volume, and it manifests as retarded growth and failure of the grafts and more mortality. However, its pathogenesis is poorly understood, and few effective interventions have been attempted. Aims. The present study aimed to delineate the critical role of oxidant stress in SFSS and protective effects of a superoxide dismutase mimetic, Mn(III) tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP), on graft function, growth, and survival in the recipient rats. Methods. Small size graft liver transplantation (SSGLT) was performed to determine the survival, graft injury, and growth. MnTBAP was administered in SSGLT recipients (SSGLT+MnTBAP). Results. Serum alanine aminotransferase levels were sustained higher in SSGLT recipients, which were correlated with an increased apoptotic cell count and hepatocellular necrosis in liver sections. Malondialdehyde content, gene expression of tumor necrosis factor alpha and interleukin 1 beta, and DNA binding activity of nuclear factor-kappa B in the grafts were increased significantly in SSGLT recipients compared with sham-operated controls. Both phosphorylated p38 mitogen-activated protein kinase and nuclear c-Jun were increased in SSGLT. All these changes were strikingly reversed by the administration of MnTBAP, with an increase in serum superoxide dismutase activity. Moreover, in situ bromodeoxyuridine incorporation demonstrated that graft regeneration was much more profound in the SSGLT+MnTBAP group than in the SSGLT group. Finally, the survival of recipients with MnTBAP treatments was significantly improved. Conclusions. Enhanced oxidant stress with activation of the p38/c-Jun/nuclear factor-kappa B signaling pathway contributes to SFSS-associated graft failure, retarded graft growth, and poor survival. MnTBAP effectively reversed the pathologic changes in SFSS-associated graft failure.
引用
收藏
页码:687 / 694
页数:8
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