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| 1 | Molecular mechanisms of liver ischemia reperfusion injury:Insights from transgenic knockout models显示文摘Ischemia reperfusion injury is a major obstacle in liver resection and liver transplantation surgery.Understanding the mechanisms of liver ischemia reperfusion injury(IRI) and developing strategies to counteract this injury will therefore reduce acute complications in hepatic resection and transplantation,as well as expanding the potential pool of usable donor grafts.The initial liver injury is initiated by reactive oxygen species which cause direct cellular injury and also activate a cascade of molecular mediators leading to microvascular changes,increased apoptosis and acute inflammatory changes with increased hepatocyte necrosis.Some adaptive pathways are activated during reperfusion that reduce the reperfusion injury.IRI involves a complex interplay between neutrophils,natural killer T-cells cells,CD4+ T cell subtypes,cytokines,nitric oxide synthases,haem oxygenase-1,survival kinases such as the signal transducer and activator of transcription,Phosphatidylinositol 3-kinases/Akt and nuclear factor κβ pathways.Transgenic animals,particularly genetic knockout models,have become a powerful tool at elucidating mechanisms of liver ischaemia reperfusion injury and are complementary to pharmacological studies.Targeted disruption of the protein at the genetic level is more specific and maintained than pharmacological inhibitors or stimulants of the same protein.This article reviews the evidence from knockout models of liver IRI about the cellular and molecular mechanisms underlying liver IRI. | Gourab Datta Barry J Fuller Brian R Davidson | 2013 | World Journal of Gastroenterology2013，19，11： | 50 |
| 2 | Haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury显示文摘AIM To investigate the hepatic microcirculatory changes due to Haemoxygenase(HO),effect of HO inhibition on remote ischemic preconditioning(RIPC) and modulation of CINC.METHODS Eight groups of animals were studied- Sham,ischemia reperfusion injury(IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion,RIPC(remote ischemic preconditioning) + IRI group,remote ischemic preconditioning in sham(RIPC + Sham),PDTC + IR(Pyridodithiocarbamate,HO donor),Zn PP + RIPC + IRI(Zinc protoporphyrin prior to preconditioning),IR-24(45 min of ischemia followed by 24 h of reperfusion),RIPC+IR-24(preconditioning prior to. After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS Velocity of flow(160.83 ± 12.24 μm/s),sinusoidal flow(8.42 ± 1.19) and sinusoidal perfusion index(42.12 ± 7.28) in hepatic IR were lower(P < 0.05) in comparison to RIPC and PDTC(HO inducer). RIPC increased velocity of flow(328.04 ± 19.13 μm/s),sinusoidal flow(17.75 ± 2.59) and the sinusoidal perfusion index(67.28 ± 1.82)(P < 0.05). PDTC(HO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity(300.88 ± 22.109 μm/s),sinusoidal flow(17.66 ± 3.71) and sinusoidal perfusion(82.33 ± 3.5) to near sham levels. Zn PP(HO inhibition) reduced velocity of flow of RBC in the RIPC group(170.74 ± 13.43 μm/s and sinusoidal flow in the RIPC group(9.46 ± 1.34). Zn PP in RIPC(60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules(769.05 ± 87.48) and sinusoids(97.4 ± 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules(219.66 ± 93.79) and sinusoids(25.69 ± 9.08)(P < 0.05). PDTC reduced neutrophil adhesion in both postsinusoidal venules(89.58 ± 58.32) and sinusoids(17.98 ± 11.01)(P < 0.05) reproducing the effects of RIPC. Zn PP(HO inhibition) increased venular(589.04 ± 144.36) and sinusoidal neutrophil adhesion in preconditioned animals(121.39 ± 30.65)(P < 0.05). IR after 24 h of reperfusion increased venular and sinusoidal neutrophil adhesion in comparison to the early phase and was significantly reduced by RIPC. Hepatocellular cell death in IRI(80.83 ± 13.03),RIPC + IR(17.35 ± 2.47),and PTDC+IR(11.66 ± 1.17) Zn PP + RIPC + IR(41.33 ± 3.07) reduced hepatocellular death. Zn PP significantly increased hepatocellular death(P < 0.05 PTDC/RIPC vs Zn PP and IR). The CINC cytokine levels in sham(101.32 ± 6.42). RIPC + sham(412.18 ± 65.24) as compared to sham(P < 0.05). Hepatic IR(644.08 ± 181.24)(P < 0.05). RIPC CINC-1 levels in the early phase(401.62 ± 78.56). And PDTC(HO inducer) CINC-1 levels in hepatic IR(413.36 ± 63.06) were significantly lower. HO inhibition in preconditioned animals with Zinc protoporphyrin increased serum CINC levels(521.81 ± 74.9)(P < 0.05). The serum CINC levels were high in the late phase of hepatic IR(15306 ± 1222.04). RIPC reduced CINC levels in the late phase of IR(467.46 ± 26.06),P < 0.05.CONCLUSION RIPC protects hepatic microcirculation by induction of HO and modulation of CINC in hepatic IR. | Niteen Tapuria Sameer Junnarkar Mahmoud Abu-amara Barry Fuller Alexander M Seifalian Brian R Davidson | 2016 | World Journal of Gastroenterology2016，22，33： | 3 |
| 3 | Probiotics in man and animals显示文摘 | Fuller R | 1989 | J Appl Bacteriol1989，66，： | 2 |
| 4 | Regulation of putative fatty acid transpoters and acyl-CoA synthetase in liver and adipose tissue in ob/ob Mice显示文摘 | Memon R A Fuller J Moser A H | 1999 | Diabetes1999，48，2： | 2 |
| 5 | FTIR spectroscopic analysis of coals and coal extracts显示文摘 | COOKE N E FULLER M O GAIKWARD R P | 1986 | Fuel1986，65，9： | 2 |
| 6 | Characteristics of wave propagation and energy distributions in cylindrical elastic shells filled with fluid显示文摘 | Fuller C R Fahy F J | 1982 | JSV1982，81，4： | 2 |
| 7 | A fuzzy approach to R&D project portfolio selection显示文摘 | Carlsson C Fuller R | 2007 | International Journal of Appraximate Reasoning2007，44，2： | 1 |
| 8 | Thea attachment of bacteria to the gastric epithelium of the pig and its importance in the microecology of the intestinal 显示文摘 | Brooker B E Fuller R | 1980 | Journal of Applied Bacteriology1980，48，： | 1 |
| 9 | Epithelial attachment and other factors controlling the colonization of the intestine of the gnotohiotic chicken by lactobacilli显示文摘 | Fuller R | 1978 | J AppliBacteri1978，45，： | 1 |
| 10 | The Characterisation and Measurement of Land Cover Change Through Remote Sensing: Problems in Operational Applications显示文摘 | Fuller R M Smith G M Devereux B J | 2003 | International Journal of Applied Earth Observation and Geoinformation2003，4，： | 1 |
| 11 | Prebiotics in man and animals显示文摘 | Fuller R | 1989 | Joumal of Applied Bacterilolgy1989，66，： | 1 |
| 12 | Sonic testing a simple nondestructive testing for verifying casting quality 显示文摘 | Fuller A G Emerson P J Rew R | 1963 | BCIRA Journal1963，，11： | 1 |
| 13 | A survey of coccidia on 43 poultry farms in Argentina 显示文摘 | McDougald L R Fuller L Mattiello R | 1997 | Avian Dis1997，41，4： | 1 |
| 14 | On possibilistic mean value and variance of fuzzy numbers 显示文摘 | Carlsson C Fuller R | 2001 | Fuzzy Sets Syst2001，122，： | 1 |
| 15 | Investigation into an outbreak of encephalomyelitis caused by a neuroinvasive porcine sapelovirus in the United Kingdom显示文摘 | SCHOCK A GURRALA R FULLER H | 2014 | Vet Microbiol2014，172，34： | 1 |
| 16 | An error analysis of failure prediction techniques derived from fracture mechanics 显示文摘 | Wiederhom S M Fuller E R Mandel J | 1976 | Journal of the American Ceramic Society1976，59，910： | 1 |
| 17 | Prebiotics,probiotics and human gutmicrobilogy显示文摘 | Fooks LJ Fuller R Gibson GR | 1999 | Int Dairy J1999，9，1： | 1 |
| 18 | Hysteresis properties of titaimagnetities: Grain-size and compositional dependence 显示文摘 | Day R Fuller M Schmidt V A | 1977 | Physics of the Earth and Planetary Interiors1977，13，4： | 1 |
| 19 | Direct comparison of levels of genetic variation among barley accessions detected by RFLPs, AFLPs, SSRs and RAPDs显示文摘 | Russell J R Fuller J D Macaulay M | 1997 | Theoretical and Applied Genetics1997，95，： | 1 |
| 20 | Active control of coupled waved propagation in fluid-filled elastic shell 显示文摘 | Brevar B J Fuller C R | 1993 | Journal of Sound and Vibration :1993，94，3： | 1 |
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