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Establishment Of The Rat Model Of Parkinson's Disease And Treatment With The Transplantation Of Induced PC-12 Cell Line

Posted on:2005-10-15Degree:MasterType:Thesis
Country:ChinaCandidate:X Z LiuFull Text:PDF
GTID:2144360122994419Subject:Zoology
Abstract/Summary:PDF Full Text Request
Parkinson's disease (PD) is characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta of the brainstem, leading to motor abnormalities. This disease, first described by James Parkinson in 1817, is a chronically progressive neurodegenerative disease, affecting at least 1% of the population over the age of 55. Fully developed PD comprises motor symptoms such as tremor, rigidity and bradykinesia (slowness of movement).At present, treatments to Parkinson's disease include drug,surgery,cell transplantation treatment and genetic therapy.The druggery therapy may improves the sufferer's symptoms such as tremor and rigidity,but it can not hold back the evolution of this disease and may cause dyskinesias or other serious syndromes.Nerve alimentation factors, anti-apoptosis medicaments and immunosuppressors can protect nerves and accelerate neuraxons' growth,but this effect only prevents dis-suffered nerve cells from denaturalization.These measures can not resolve the function holdback resulting in loss of nerve cells and decrease of dopamine. So those therapies are not of significance to those sufferers who have clinic symptoms. Due to heavy hurt of the operation and its limited application, surgery is not an ideal therapeatic strategy.Parkinson's disease (PD) is characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta, leading the level of dopamine descending and a series of symptoms.Transplanting cells that can excrete dopamine into the substantia nigra-striatum system may reinforce dopamine in the striaturn and achieve the purpose of the therapy.Pheochromocytoma cells are similar to adrenalmedulla cells.Those cells also can excrete tyrosine hydroxylase.When treated with nerve growth factor(NGF),PC-12 cells can transform to sympathetic nerve shape cells. The cellular differentiation make PC-12 cells more similar to. nerve cells in the aspest of morphology, physiology, biochemistry and function.So transplanting the NGF induced PC-12 cell line into the striatum ,can alleviate symptoms of Parkinson's disease.In this experiment,I established 6-hydroxydopamine (6-OHDA) lesioned rats model as model of rat parkinson's disease ,then transplanted the NGF induced PC-12 cells into striarum by stereotaxic microinjection.and observed the improvement of rat's behaviors and condition of transplanted PC-12 cells.Result:1. 27 of 49 rats showed steady left apormorphine-induced rotation(55.1%),and the rotation rate was above 210r/30min, which indicated that rats were successful PD models.PD rats displayed abnormal behaviors such as trembling,moving stiffly ,sniffing peeking for food ,rail erection ,et al. 7 successful PD rat models after operation were randomly chosen. The immunohistochemical staining showed significant loss of TH-positive neurons in the injection place compared with opposite side . And 5 success PD rat models after operation were randomly chose . The western blot result showed the tyrosine hydroxylase content has significant fall compared with opposite side.2.Inducement the PC-12 cells last 7 days using NGF (50ng/ml).In inducement forepart cells gradually occur at some changes such as smooth, appearance of appurtenances in cells and hinge on cell membrane. Follow the inducement time, the characters of long inducement appear such as ceasing increase and appearance of cell protuberance.3. The improve of apormorphine-induced rotation of the operation group is significant compared with the control group. The immunohistochemical staining showed TH-positive neurons in striatum. The western blot result showed the tyrosine hydroxylase has exist in striatum. The result of immunohistochemical staining and western blot in the control group has not significant positive signal.Conclusion:1. Adopt 6-OHDA to Establish the PD model.The successful ratio is 55.1%. The immunohistochemical staining showed significant loss of TH-positive neurons compared with opposite side . The western blot result showed the tyrosine hydroxylase content...
Keywords/Search Tags:Parkinson's disease, transplant treatment, NGF(nerve growth factor), pheochromocytoma cells
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