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Treatment Effects Of Injecting IGF-1 By Fenestration On Gentamicin-induced Hearing Loss Guinea Pigs

Posted on:2008-04-15Degree:MasterType:Thesis
Country:ChinaCandidate:H ChenFull Text:PDF
GTID:2144360218461535Subject:Otorhinolaryngology
Abstract/Summary:PDF Full Text Request
Sensorineural hearing loss is one of common diseases inOtorhinolaryngology-Head and Neck Surgery; there are more than 20 million deafpatients in the nation. Lack of blood, virus infection, ototoxic deafness, anddegenerate pathological changes of ageness and so on are the public recognizedcauses of disease. Pathological changes are mainly result from hair cellsdamnification, organic changes in spiral ganglion, support cells and nervous twigs. Agood few of treatments do not get effectness, so till now it has no good method.Patients who are irresponsive to the medicine treatments can only get help with thehearing aid or do the cochlear implant.In recent years, some researches reported the internal vestibule and cochlear haircells of mammalians, even human, were possibly reproduced after injured. Somesensorineural hearing loss in both ears patients in clinic, after genetamicin treatment,improved the audition 15-20Db in low frequent distict after ceasing the medicine 3weeks, and improved 10-25Db in all frequent distict after 3 months. All the aboveproves that the functions of vestibules and cochlears of human could be possibly rebuilt as the hair cells of inner ears of birds do. At the same time, many researchesin recent years proved that using the growth-factor substance can boost the restoringand rebuilding of the harmed nerves and hair cells of inner ears in outside-bodycultivated cochlear Corti organs. The news brings galactic hope for the hearing losspatients, but the trials carried on mammalians are still failed.Insulin-like growth factor (IGF) is one kind of proteins abroadly existing inmany apparatuses and organs. IGF obtains the name because that its gene frame ishighly affinal with insulin, and also it has similar effect as insulin. Especially IGF-1has the same important biological effects as insulin in boost the growth of economy,the organic restoring, substance and nourition metabolization; promote thepolarization and split of cells and so on. Biological function of IGF-1 can carry outthrough autocrine and paracrine, as well through the special isomerism acceptor oftarget cell. IGF-1 is the indispensable accommodate factor during the normal growthof inner ears. It can accommodate multiplication or death of cochlear, growth andpolarization of nerve cells. So it is conjectured that IGF-1 can be used as apromising medicine to boost the rebuilding of hair cells and the restoring of acousticnerve, to cure heating obstacle.Cochlear becomes a comparative close micro-entironment, as the doubleobstacles exist in the inner ear—the bone frame of cochlea and blood-braid as wellas blood-labyrinth barriers. As a result, most of protein growth factors and nervenutrition medicines may hardly enter inner ear efficiently, bringing tremendousdifficulty in curing ear diseases. Recently, inner ear scala tympani Fenestration arethe main approach to lead the gene-growth factor, cell-growth factor and so on tothe inner ear. Base on Fenestration, to control the aperture of fenestration in thescope of not influencing audition is micro-aperture technique. After reseached,Stover believed that injecting virus holder through scala tympani drill and round window theca did not impact the audition. Our department has done more than 150cases of electronic cochlear transplantation, which is the application of scalatympani Fenestration and micro-aperture technique, and a useful reference for thisresearch. Zhao Changding studied the evoked potential using cochlearmicro-aperture techniqu, and found out most of the guinea pigs lossed 0-5dB, butgot normal within one to two weeks. Gao Pengfei believed the aperture of scalatympani fenestration was about 0.6 mm, and after restored, it did not have evidenceeffect on hearing threshold and hearing hair cells. So we can basically ignore theinfluence on the hearing of the surgery if injecting IGF-1 into inner ears throughcochlear micro-aperture technique to cure sensorineural deafness.ObjectiveStudy the treatment effect of IGF-1 for sensorineural deafness of animal mode(GM-induced hearing loss guinea pigs), by injecting IGF-1 into inner ears throughscala tympani fenestration and micro-aperture technique.Methods1. Materials50 healthy mottle and black-eyed guinea pigs (rank 2nd, provided by AnimalExperiment Center of Zhujiang Hospital, Southern Medical Universtiy), weightranging from 250 to 300g, of either gender, with sensentive auricles, entire tympanicmembrane, excluding abnormal hearing guinea pigs by ABR.2. Experiment Process:Three main processes:(1)50 guinea pigs were randomly divided into two groups: Group A (control group,25), Group B (GM-induced hearing loss guinea pigs, 25). Group A were fed undernormal condition, while guinea pigs of Group B were muscular injected GM for continuous four weeks and monitored by ABR.(2)Improve the research method, study guinea pigs ABR test consciousness instead ofnarcotism to reduce sudden death rate of guinea pigs (especially GM-induced hearingloss guinea pigs), ensure the success of study.(3) After built-up the mode, chose 20 guinea pigs from Group A, then divided intoGroupⅠ(normal group, 10) and GroupⅡ(surgery group, 10) randomly; GroupⅠwere fed under normal condition. GroupⅡwere conducted scala tympanifenestration, with a view to get known the affect on the hearing and cochlea organs ofguinea pigs.(4) Chose 20 guinea pigs from Group B, then divided into GroupⅢ(GM group, 10)and GroupⅣ(IGF-1 group, 10); GroupⅢand GroupⅣwere conducted scalatympani fenestration, GroupⅢwere injected article lymph, GroupⅣwere injectedIGF-1, to study the therapy effect of IGF-1 to GM-induced hearing loss guinea pigs.Each part was conducted Statistics analyszed (all datas were recorded by auditiontesting system, using SPSS13.0 to process datas and statistica analysed by reletivemethods) and Morphological observation (conduct morphological study through SEMand TEM).Results1.ABR RT has prominent difference (P<0.01) between Group A (normal controlgroup) and Group B (GM-induced hearing loss group) which had been injected GMafter 28 days.2.It did not have prominent difference (P>0.05) in ABR RT orⅠ,ⅢPL undernarcotism or consciousness of Group A (normal control group).3. ABR RT has no prominent difference (P>0.05) between GroupⅠand GroupⅡ7days after surgery. ABR RT has no prominent difference (P>0.05) in GroupⅡone hour before and 7 days after surgery.4. ABR RT has prominent difference (P<0.01) between GroupⅢand GroupⅣ14days after surgery. ABR RT has prominent difference (P<0.01) in GroupⅣbeforeand 14 days after surgery.Conclusion1. GM is ototoxic, but less kidney toxin compared to other AmAns, cheap price, wideuse in clinic, and easily obtained, an ideal medicine to conduct sensorineural deafnessof animal mode.2. ABR test is an ideal index to value the audition change of guinea pigs impersonally,owning to stable and easy to dispute wave, record conveniently, analyzing thepathology of auditory brainstem and nearby functions through RT, PL, IPL, AP and soother of wave.3. Hearing-test system developed by Professor Guo Menghe is excutitude andcredible, easy to conduct, so it meets the needs of animal audition test.4. ABR test of guinea pigs conducted under consciousness, has the followingadvantages compared to under under narcotism: accurate data, easy handle, reducingdeath rate of guinea pigs, and more closer to the normal condition of guinea pigs.5. Scala tympani fenestration and micro-aperture technique are easy handle and safe,not affect the function of cochlea, which are likely to be the effective treatment tohearing loss and other inner ears diseases.6. IGF-1 can promote and support the regeneration of hair cells of inner ears, whichcan be the medicine for sensorineural deafness, testing in clinic trials.
Keywords/Search Tags:IGF-1, guinea pigs, anesthesia, GM, fenestration
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