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Study Of The Significance And Expression Of Nerve Growth Factor And Its Receptors During Mandible Fracture Healing

Posted on:2006-11-13Degree:MasterType:Thesis
Country:ChinaCandidate:L M YuFull Text:PDF
GTID:2144360155452818Subject:Oral and clinical medicine
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At clinic the incidence of fracture is very large ,there arecomparative partial fractures (about 5%-10% of the total of fractures) willoccur fracture delayed healing or nonunion though the most fracture canheal up triumphantly. Therefore it is a challenge in medical field toaccelerate the fracture healing and avoid occurring delayed healing ornonunion. With the attention on the affection of nerve factors duringfracture healing is more and more ,the NGF which can keep nerve celllive ,induce sense and sympathetic nerve fiber growth to targetorganizations received more and more attention.Nerve growth factor(NGF) is a kind of polypeptide, which couldyield many kinds biological effects by combining with special receptor ontarget cell surface. There are two kind of receptor proteins of NGF ,oneis high affinity NGF receptor that is slow on combinative motivity. TheNCF high affinity receptor, which is a kind of tyrosine kinase receptorthat is coded by original cancer gene-trk, is called trkA. The other NGFreceptor protein is a low affinity receptor which is p75 for short. It canquickly combine with mate at combine dynamics but there is notperceptible cytology reaction when combine with it.p75 can regulate Trkreceptor's sensitivity to NGF as a assistant factor. Recent 10 yearsforeign scholars have many meticulous studies on the affection of NGFto fracture healing and the type of bone forming cell surface receptor, theresults of reports are not consistent. There are not analogous reports onthe affection of NGF during fracture healing in our country. To discuss the expression of nerve growth factor (NGF) and nervegrowth factor receptor (NGFR ) during fracture healing and to discussthe influence and affection of NGF during fracture healing . Fartherelucidate the facture healing way after firm internal fixation. A total of 32rabbits were studied in this experiments. All animals were separated into8 group randomly :control ,1d, 3d, 5d, 7d,14d,21d,28d. Experimentalanimals compare with themselves, right side is experimental side andleft is control side. Establish right mandible fracture model , then fixedthem with titanium splint immediately. After that take food normally, theanimals of experimental group were executed by neck artery perfusionwith polyformaldehyde at 1d,3d,5d,7d,14d,21d,28d. Double mandiblesand soft organizations around them were cut and made into boneorganization slice up after putting off calcium, then delt with HE, NGF ,TRKA and P75 immunohistochemical coloration. We observed thecomplexion of fracture concrescence after firm internal fixation atdifferent time through microscope and observed the distributing andexpression of NGF,TRKA and P75 in normal bone organization andbone callus ,and the expression intensity at different time. We also madeuse of image analysis and statistics analysis. In our study every group animals could take food and movementnormally in the first 3 days after operation. When we cut the mandibleswe could find every animal's splint did not loose and break .The rightmandible lateral radiograph ,which were taken at 5d,7d,14d,21d,28dafter fracture ,show that abbreviated titanium splints were well fixed ,fracture line well contraposed and there were renascent "V"shape bonecallus at mandible underside in 21d and 28d group. Fracture callus only occured at the gena side and underside atfracture location and the callus were very thin but that did not occur atlingual side .The zone of fracture closely cicatrized at 7d and the mainlytype of concrescence was cranny bone concrescence. At the zone offracture the osteogentic cells outside periosteum multiplicated intoosteoblast and made priority to intramembranaous ossification, and alsohave a few endochondral ossification . NGF had light immunostaining in unfracture group , mainly locatedin osteogentic cells and skeletal muscles. When mandible fractured NGFincreased rapidly and at fibroblast,osteoblast and marrow stromal cellsNGF coloration manifested to be strong positive,some bone cells in thezone of fracture manifested to be positive, brown granules located atcytoplasm nearby karyotheca , NGF in cartilage cells which occuredsubsequently also expressed strong positive When osteoblast weregradually enwrapped by bone girders NGF expressed weak positive ornegative. Through the Computer Image Analyzing System detection andstatistics analysis NGF achieved pinnacle at 3-5d after fracture, that hadprominent difference (P<0.01) except 28d group and normal group. Thatindicated that NGF maybe have some relationship with bone normalmetabolization; when fracture happened NGF appeared strong positiveexpression in all bone pattern cells ,that prefigured that NGF had aclosely connection with the activation and differentiation of bone patterncells and the rebuilding of bone scab.It might further activateBMP,TGF,IGF and so on ,and to accomplish bone restoration together. The expression of TRKA and P75 in normal bone organizations wasweak but in fracture group that of TRKA in almost all bone pattern cellswas positive and at 7d the expression achieved pinnacle, at 21d theexpression in cartilage cells was also strong positive. TEKA receptorswere activated by NGF, firstly aroused receptor molecules double-converged at cell surface then tyrosine kinase receptor wereactivated ,that tyrosine kinase receptor made the of receptor oneselfconfiguration self-phosphatify and induce cells polarization byaccommodating gene expression. P75 receptor's expression wasrelatively weak and at 7d that achieved pinnacle. And P75 hadamplificatory function to the combination between TRK and NGF as aregulation factor. The mutual function between the two receptors madethe low consistence NGF could combine with cell surface receptor. By the continuous observations of fracture concrescence courseafter firm inner fixation in rabbit mandible fracture, we found whenmandible fracture happened the adoption of firm inner fixation changedthe traditional manner of fracture concrescence (2-period concrescence),the local acestoma and cartilages were very little. It can reduce theincidence rate of infection and bone incontinuity in clinic. The mainconcrescence manner of mandible fracture is intramembranaousossification,, but there were still typical endochondral ossification in thelocation of large fracture clearance and severe wound. NGF expressed in both non-fracture and fracture of mandible that...
Keywords/Search Tags:Nerve growth factor, TrkA, p75, Fracture healing
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