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The Effects Of Irradiation By Gamma Knife And Methylprednisolone (MP) On Expression Of Connexin43 (Cx43) And GFAP In Cultured Rat Astrocytes

Posted on:2010-10-10Degree:MasterType:Thesis
Country:ChinaCandidate:M WeiFull Text:PDF
GTID:2144360275992416Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective:γ-knife radiosurgery has become an important component of morden neurosurgery.At current conditions of planning system,it is difficult to achieve the target area completely except for normal brain tissue.So,the nerve tissue around the lesion will still be affeccted by radiosurgery treatment,resulting in normal nerve tissue radiation injury in some patients after treatment.The exact mechanism is unclear.Many radiationsurgery tests have proven gliosis are the mainform of radiation injury.The radiation injury can increase the number of glia cell and GFAP immunohistochemical stainning expression,both the severity associated.To date,the mechanism of the occurrence of radiation injury is not yet clear.Gap junction protein(connexin,Cx) is considered to be a tumor suppressor gene family and can inhibit cell growth and proliferation,its mechanism may be related to the role of non-communication.Recent studies have shown that the Cx43 expression reduction ofen leads to abnormal growth of cell or occurring of tumor.Glucocorticoids have the effect of anti-inflammatory and reduce the edema and have been widely used in the treatment of nervous system radiation injury especially in radiation-induced cerebral edema.The pharmacological mechanisms are extremely complex,which include inhibiting cell division and proliferation.Such a role may be related to Cx expression in the existence of common signal transduction pathway.The experimental study shows how the glial cell Cx43 and GFAP expression changes in brain injury after gamma knife irradiation and how the application of glucocorticoids affect Cx expression.We have preliminary study of the inter-astrocyte gap junction changes at radiology brain,as well as the possible mechanisms of tissue gliosis and radiation injury.This study explores new treatment of radiation injury after gamma knife and provides a basis and reference for further clinical application and research.Methods:Astrocytes from rats were cultured and irradiated by gamma knife.A total of rat astrocytes were divided into 2 groups:control group and gamma knife—treatment group.The gamma knife—treatment group was further divided into nine subgroups at different doses(4~36Gy),and the changes in GFAP and Cx43 expression were detected by immunofluorescence methods 72h after radiation by Gamma knife.A total of rat astrocytes by gamma knife at single dose of 32Gy were divided into l~40μg/ml groups and control group.The every group were further divided into five subgroups at different time(36~120h).MP(1-40μg) was added into the media of 1~40μg/ml groups.After 36~120h Cx43 and GFAP immunoreactivity was observed.Results:Compared with the normal control group,GFAP expression in a dose-dependent manner was found in the gamma knife irradiation group,its expression was elevated at 16Gy more than that in normal group,approaching its peak value in 32Gy group,and the levels of gamma knife irradiation group were statistically diferent from those in the normal control group(P<0.05).Cx43 expression in a dose-dependent manner was lowered.It became lower than in normal group at 12Gy,reached the lowest In 32Gy group.In 20~30μg/ml group MP induced upregulation of Cx43 expression in a time-dependent manner,meanwhile compared with the control group the levels of GFAP expression in MP treatment group was decreased(P<0.05) all time.Though GFAP was increased in a time-dependent manner.GFAP expression reached the highest sooner than control group,which lower compared with control group(P<0.05).Conclusion:The expression of GFAP can be increased and expression of Cx43 are depressed_after gamma knife treatment.Cx43 may play a important role in Astrocytic proliferation and brain radiation injury after gamma knife radiosurgery as well as GFAP did.The results show that the expression of GFAP are depressed by MP and expression of Cx43 can be increased after gamma knife treatment.MP may prevent the increase of the content of GFAP.
Keywords/Search Tags:gamma knife, methylprednisolone, connexin glial, fibrillary acid protein, astrocytes, radiation injury
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