Triiodothyronine enhances the regenerative capacity of the liver following partial hepatectomy

被引:41
作者
Malik, R [1 ]
Mellor, N [1 ]
Selden, C [1 ]
Hodgson, H [1 ]
机构
[1] UCL Royal Free & Univ Coll Med Sch, Dept Med, Ctr Hepatol, London NW3 2PF, England
关键词
D O I
10.1053/jhep.2003.50001
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
This study investigates the effects of administering a primary mitogen, triiodothyronine (T-3), at the time of 70% partial hepatectomy (PH) in the rat, thus combining the 2 distinct pathways of liver growth: direct hyperplasia and compensatory regeneration. T-3 enhances the proliferative response of hepatocytes within the liver following PH. Flash bromodeoxyuridine (BrdU) labeling showed a cell proliferation index 24 hours after PH alone of 26.5% +/- 2.8%; when T-3 was administered at PH, it increased to 39.5% +/- 5.0% (P <.01 compared with PH alone). Continuous BrdU labeling performed every 6 hours between 15 and 72 hours following surgery showed an index of 84.0% +/- 4.0% when T-3 was administered at PH compared with 71.0% +/- 4.0% with PH alone (P <.01 compared with PH alone). This increase in cell proliferation resulted in a larger liver mass at 4 days in rats receiving T-3 at PH compared with PH alone (P <.05 compared with PH alone). The difference in liver mass was matched with corresponding increases in total DNA and total protein levels as well as cell division, as confirmed by the frequent demonstration of twin daughter cells on histology. In conclusion, this study shows that a single dose of T-3 enhances the regenerative capacity of the liver following PH. The ability to enhance cell proliferation during compensatory hyperplasia following PH could be therapeutically valuable if applicable to humans.
引用
收藏
页码:79 / 86
页数:8
相关论文
共 29 条
[1]   REGULATION OF HEPATIC GROWTH [J].
ALISON, MR .
PHYSIOLOGICAL REVIEWS, 1986, 66 (03) :499-541
[2]  
BUCHER NLR, 2000, INT REV CYTOL, P230
[3]   CONTROLLED DEATH (APOPTOSIS) OF NORMAL AND PUTATIVE PRENEOPLASTIC CELLS IN RAT-LIVER FOLLOWING WITHDRAWAL OF TUMOR PROMOTERS [J].
BURSCH, W ;
LAUER, B ;
TIMMERMANNTROSIENER, I ;
BARTHEL, G ;
SCHUPPLER, J ;
SCHULTEHERMANN, R .
CARCINOGENESIS, 1984, 5 (04) :453-458
[4]  
COLUMBANO A, 1985, LAB INVEST, V52, P670
[5]   Liver regeneration .8. Liver regeneration versus direct hyperplasia [J].
Columbano, A ;
Shinozuka, H .
FASEB JOURNAL, 1996, 10 (10) :1118-1128
[6]  
CRESSMAN DE, 1994, J BIOL CHEM, V269, P30429
[7]   Cytokine regulation of liver injury and repair [J].
Diehl, AM .
IMMUNOLOGICAL REVIEWS, 2000, 174 :160-171
[8]   Liver regeneration [J].
Fausto, N .
JOURNAL OF HEPATOLOGY, 2000, 32 :19-31
[9]   Retroviral gene transfer to the liver in vivo during tri-iodothyronine induced hyperplasia [J].
Forbes, SJ ;
Themis, M ;
Alison, MR ;
Selden, C ;
Coutelle, C ;
Hodgson, HJF .
GENE THERAPY, 1998, 5 (04) :552-555
[10]   Synergistic growth factors enhance rat liver proliferation and enable retroviral gene transfer via a peripheral vein [J].
Forbes, SJ ;
Themis, M ;
Alison, MR ;
Sarosi, I ;
Coutelle, C ;
Hodgson, HJF .
GASTROENTEROLOGY, 2000, 118 (03) :591-598