RETRACTED: Fat-derived hormone adiponectin combined with FTY720 significantly improves small-for-size fatty liver graft survival (Retracted Article)

被引:25
作者
Man, K [1 ]
Zhao, Y
Xu, A
Lo, CM
Lam, KSL
Ng, KT
Ho, JWY
Sun, CK
Lee, TK
Li, XL
Fan, ST
机构
[1] Univ Hong Kong, Ctr Study Liver Dis, Pokfulam, Hong Kong, Peoples R China
[2] Univ Hong Kong, Dept Surg, Pokfulam, Hong Kong, Peoples R China
[3] Univ Hong Kong, Dept Med, Pokfulam, Hong Kong, Peoples R China
[4] China Med Univ, Affiliated Hosp 2, Dept Surg, Shenyang, Peoples R China
关键词
anti-steatosis; cell survival signaling; hepatic microcirculation; liver transplantation; marginal graft;
D O I
10.1111/j.1600-6143.2005.01201.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
Owing to the discrepancy between organ donation and the demand for liver transplantation, expanding the liver donor pool is of vital importance. However, marginal liver grafts, such as small-for-size and/or fatty grafts, were associated with primary graft nonfunction or poor function. Therefore, novel combination therapies to rescue small-for-size fatty liver grafts should be investigated. In this study, we applied a combination therapy using a fat-derived hormone adiponectin (anti-steatosis) plus immunomodulator FTY720 (anti-inflammatory) in a rat liver transplantation model using small-for-size fatty liver grafts, and investigated the underlying protective mechanism such as anti-steatosis, intra-graft energy metabolism, hepatic microcirculatory changes, cell signaling cascades for survival, apoptosis and inflammation. The current study demonstrated that even a single treatment of adiponectin or FTY720 improved the 7-day graft survival from 0% to 62.5% (p = 0.001). The combination therapy significantly increased the 7-day graft survival rate to 100% by remarkable attenuation of graft steatosis and acute phase inflammatory response, significant activation of cell survival Akt pathway and maintenance of intra-graft adenosine triphosphate metabolism and improvement of hepatic microcirculation. In conclusion, the fat-derived hormone adiponectin combined with FTY720 might be a novel combination drug therapy for prevention of small-for-size fatty liver graft injury.
引用
收藏
页码:467 / 476
页数:10
相关论文
共 29 条
  • [11] HAGA S, 2005, J HEPATOL
  • [12] Distinct intragraft response pattern in relation to graft size in liver transplantation
    Liang, TB
    Man, K
    Lee, TKW
    Tsui, SHT
    Lo, CM
    Xu, X
    Zheng, SS
    Fan, ST
    Wong, J
    [J]. TRANSPLANTATION, 2003, 75 (05) : 673 - 678
  • [13] FK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway
    Man, K
    Lee, TK
    Liang, TB
    Lo, CM
    Fung, PCW
    Tsui, SH
    Li, XL
    Ng, KT
    Fan, ST
    [J]. ANNALS OF SURGERY, 2004, 240 (01) : 159 - 168
  • [14] Intragraft gene expression profiles by cDNA microarray in small-for-size liver grafts
    Man, K
    Lo, CM
    Lee, TKW
    Li, XL
    Ng, IOL
    Fan, ST
    [J]. LIVER TRANSPLANTATION, 2003, 9 (04) : 425 - 432
  • [15] Graft injury in relation to graft size in right lobe live donor liver transplantation - A study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression
    Man, K
    Fan, ST
    Lo, CM
    Liu, CL
    Fung, PCW
    Liang, TB
    Lee, TKW
    Tsui, SHT
    Ng, IOL
    Zhang, ZW
    Wong, J
    [J]. ANNALS OF SURGERY, 2003, 237 (02) : 256 - 264
  • [16] Liver transplantation in rats using small-for-size grafts - A study of hemodynamic and morphological changes
    Man, K
    Lo, CM
    Ng, IOL
    Wong, YC
    Qin, LF
    Fan, ST
    Wong, J
    [J]. ARCHIVES OF SURGERY, 2001, 136 (03) : 280 - 285
  • [17] Single-center analysis of the first 40 adult-to-adult living donor liver transplants using the right lobe
    Marcos, A
    Ham, JM
    Fisher, RA
    Olzinski, AT
    Posner, MP
    [J]. LIVER TRANSPLANTATION, 2000, 6 (03) : 296 - 301
  • [18] Adiponectin protects LPS-induced liver injury through modulation of TNF-α in KK-Ay obese mice
    Masaki, T
    Chiba, S
    Tatsukawa, H
    Yasuda, T
    Noguchi, H
    Seike, M
    Yoshimatsu, H
    [J]. HEPATOLOGY, 2004, 40 (01) : 177 - 184
  • [19] Technique for expanding the donor liver pool: Heat shock preconditioning in a rat fatty liver model
    Mokuno, Y
    Berthiaume, F
    Tompkins, RG
    Balis, UJ
    Yarmush, ML
    [J]. LIVER TRANSPLANTATION, 2004, 10 (02) : 264 - 272
  • [20] Ischemic preconditioning protects the steatotic mouse liver against reperfusion injury: an ATP dependent mechanism
    Selzner, N
    Selzner, M
    Jochum, W
    Clavien, PA
    [J]. JOURNAL OF HEPATOLOGY, 2003, 39 (01) : 55 - 61