|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | m TOR signaling in liver regeneration: Rapamycin combined with growth factor treatment显示文摘AIM: To investigate the effects of mammalian target of rapamycin(mT OR) inhibition on liver regeneration and autophagy in a surgical resection model.METHODS: C57BL/6 mice were subjected to a 70% partial hepatectomy(PH) and treated intraperitoneally every 24 h with a combination of the m TOR inhibitor rapamycin(2.5 mg/kg per day) and the steroid dexamethasone(2.0 mg/kg per day) in phosphate bufferedsaline(PBS) or with PBS alone as vehicle control. In the immunosuppressant group, part of the group was treated subcutaneously 4 h prior to and 24 h after PH with a combination of human recombinant interleukin 6(IL-6; 500 μg/kg per day) and hepatocyte growth factor(HGF; 100 μg/kg per day) in PBS. Animals were sacrificed 2, 3 or 5 d after PH and liver tissue and blood were collected for further analysis. Immunohistochemical staining for 5-Bromo-2'-deoxyuridine(Brd U) was used to quantify hepatocyte proliferation. Western blotting was used to detect hepatic microtubule-associated protein 1 light chain 3(LC3)-Ⅱ protein expression as a marker for autophagy. Hepatic gene expression levels of proliferation-, inflammation- and angiogenesisrelated genes were examined by real-time reverse transcription-polymerase chain reaction and serum bilirubin and transaminase levels were analyzed at the clinical chemical core facility of the Erasmus MC-University Medical Center.RESULTS: m TOR inhibition significantly suppressed regeneration, shown by decreased hepatocyte proliferation(2% vs 12% Brd U positive hepatocyte nuclei at day 2, P < 0.01; 0.8% vs 1.4% at day 5, P = 0.02) and liver weight reconstitution(63% vs 76% of initial total liver weight at day 3, P = 0.04), and furthermore increased serum transaminase levels(aspartate aminotransferase 641 U/L vs 185 U/L at day 2, P = 0.02). Expression of the autophagy marker LC3-Ⅱ, which was reduced during normal liver regeneration, increased after mT OR inhibition(46% increase at day 2, P = 0.04). Hepatic gene expression showed an increased inflammation-related response [tumor necrosis factor(TNF)-α 3.2-fold upregulation at day 2, P = 0.03; IL-1Ra 6.0-fold upregulation at day 2 and 42.3-fold upregulation at day 5, P < 0.01] and a reduced expression of cell cycle progression and angiogenesis-related factors(HGF 40% reduction at day 2; vascular endothelial growth factor receptor 2 50% reduction at days 2 and 5; angiopoietin 1 60% reduction at day 2, all P ≤ 0.01). Treatmentwith the regeneration stimulating cytokine IL-6 and growth factor HGF could overcome the inhibitory effect on liver weight(75% of initial total liver weight at day 3, P = 0.02 vs immunosuppression alone and P = 0.90 vs controls) and partially reversed gene expression changes caused by rapamycin(TNF-α and IL-1Ra levels at day 2 were restored to control levels). However, no significant changes in hepatocyte proliferation, serum injury markers or autophagy were found.CONCLUSION: mT OR inhibition severely impairs liver regeneration and increases autophagy after PH. These effects are partly reversed by stimulation of the IL-6 and HGF pathways. | Suomi MG Fouraschen Petra E de Ruiter Jaap Kwekkeboom Ron WF de Bruin Geert Kazemier Herold J Metselaar Hugo W Tilanus Luc JW van der Laan Jeroen de Jonge | 2013 | World Journal of Transplantation2013，3，3： | 6 |
| 2 | Ki-67 immunoquantitation in cervical intraepithelial neoplasia(CIN):a sensitive marker for grading显示文摘 | Kruse A J Baak J P De Bruin P C | 2001 | J Pathol2001，193，1： | 1 |
| 3 | Enhancement of the complement activating capacity of 17-1A mAb to overcome the effect of membrane-bound complement regulatory proteins on colorectal carcinoma显示文摘 | Gelderman K A Kuppen P J Bruin W | 2002 | Eur J Immunol2002，32，1： | 1 |
| 4 | Effects of a porcine reproductive and respiratory syndrome virus infection on the development of the immune response against pseudorabies virus显示文摘 | M G M De Bruin Samsom J N | 2000 | Veterinary Immunology and Immunopathology2000，76，： | 1 |
| 5 | Age-related changes in the ultrastructure of the resting follicle pool in human ovaries 显示文摘 | De Bruin J P Dorland M Spek E R | 2004 | Biology of Reproduction2004，70，2： | 1 |
| 6 | Long-term outcome of open or endovascular repair of abdominal aortic aneurysm显示文摘 | De Bruin JL Baas AF Buth J | | 0，，20： | 1 |
| 7 | Enhancement of gas-liquid mass transfer by a dispersed second liquid phase显示文摘 | Bruining W J Joosten G E H Beenackers A A C M | 1986 | Chem Eng Sci1986，41，7： | 1 |
| 8 | Site-directed mutagenesis and oxygen isotope incorporation studies of the nucleophilic aspartate of haloalkane dehalogenase 显示文摘 | Pries F Kingma J Pentenga M van Pouderoyen G Jeronimus-Stratingh CM Bruins AP Janssen DB | 1994 | Biochemistry1994，33，： | 1 |
| 9 | In -situ CO2 -coal reaction in view of carbon dioxide storage in deep unminable coal seams 显示文摘 | Mazumder S Hemert P V Bruining J | 2006 | Fuel2006，，85： | 1 |
| 10 | knowledge transfer between fields of sci- ence显示文摘 | Rinia E J Measuring van Leeuwen T N Bruins E E W | 2002 | Scientometrics2002，54，3： | 1 |
| 11 | Moderate-to-heavy alcohol intake is associated with differences in synchronization of brain activity during rest and mental rehearsal显示文摘 | Eveline A de Bruin Cornelis J Stamb Suzanne Bijl | 2006 | International Journal of Psychophysiology2006，60，3： | 1 |
| 12 | The scintillation method tested over a dry vineyard area显示文摘 | De Bruin H A R Van Den Hurk B J J M Koshiek W | 1995 | Boundary-Layer Meteorology1995，76，： | 1 |
| 13 | Direct evidence for epithelial-mesenchymal transitions in breast cancer 显示文摘 | Trimboli A J Fukino K de Bruin A | 2008 | Cancer Res2008，68，3： | 1 |
| 14 | Modeling of gas flow and temperature fields in underground coal fires显示文摘 | Huang J J Bruining J Wolf K-H | 2001 | Fire Safety Journal2001，36，5： | 1 |
| 15 | Hemodynamic effects of leg crossing and skeletal muscle tensing during free standing in patients with vasovagal syncope 显示文摘 | van Dijk N de Bruin IGJ Gisalf J | 1998 | J Appl Physiol1998，98，： | 1 |
| 16 | Food Security in China and Contingency Planning: the Significance of Grain Reserves 显示文摘 | Bruins H J Bu F | 2006 | Journal of Contingencies & Crisis Management2006，，3： | 1 |
| 17 | Design and synthesis of biodegradable networks composed of non-toxic building blocks 显示文摘 | Bruin P Veenstra G J Nijenhuis A J | 1988 | Die Makromolekulare Chemic Rapid Communications1988，9，8： | 1 |
| 18 | Biodegradable three-dimensional networks of poly ((dimethylamino) ethyl methacrylate): Synthesis, characterization and in vitro studies of structural degradation and cytotoxicity显示文摘 | Bruining M J Harriet G T | 2000 | Biomaterials2000，21，6： | 1 |
| 19 | Treatment-related risk factors for premature menopause following Hodgkin lymphoma 显示文摘 | De Bruin ML Huisbrink J Hauptmann M | 2008 | Blood2008，111，1： | 1 |
| 20 | A system to measure surface fluxes of momentum,sensible heat,water vapour and carbon dioxide显示文摘 | Moncrieff J B Massheder J M Bruin D H | 1997 | J Hydrol1997，189，： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员