| Objective: Multiple sclerosis (MS) is an inflammatory demyelination disease of the central nervous system (CNS) ,the young wonmen more susceptible with this disease,that clinical syndrome appears relapsing and progressive neurological impairment,and at last,make the physical disorder,decline the quality of life. But,until now, the pathogenesis of MS is still unclear, and there also has no specific remedy for it. The experts think it involved hereditary,immunity,viral infection and so on,which means much reason and one result.Although the special etiological factor is uncertain,oxidative stress is the close relationship with the happen and development of multiple sclerosis.So researching oxidative stress,choosing free radical scavenger,stoping the amply action,may be the cure target.Peroxiredoxins,a new antioxygen protein,which was discoved tens years , molecular weight 25-30KD , belongs to antioxygen protein superfamily.Comparing to other antioxygen protein .Prx2 is a number of this family,especially in central nervous system ,having the function of protection neurons,and taking the attention of experts.Nuclear factor kappa B,NF-κB ,discovered by Sen and Baltimore,in 1986,first detected in B homeocyte,can idiobind withκlight chain of immune globulin,and widespread in cell。NF-κB lives in Gliocyte,a immunity cell in CNS,and keep inactivet in the resting state. Oxidative stress is activation signals,then NF-κB enter to nucleus,bind with theκB array of Prx2,enhance the gene expression ,protect the body from oxidative stress.Edaravone ,a micromolecule,is a free radical scavenger, and has been used as an anti-oxidative agent in acute ischemic brain disorders. Recently, there are some observations suggest that the active involvement of microglia may have a pathological role in both demyelinating and neurodegenerative disorders. Thus, agents that suppress the production of NO and ROS by activated microglia may be useful in the treatment of such pathological conditions. It may function as a neuroprotective agent counteracting oxidative neurotoxicity arising from activated microglia,as occurs in either inflammatory or neurodegenerative disorders of the central nervous system.In this experience,through the animal model of multiple sclerosis -experimental autoimmune encephalomyelitis, EAE,we give intervention drug -Dexamethasone ,Edaravone,compare the morbility, behavior,pathology of brain and changing of index-Prx2 and NF-κB.Then research the pathogenesis,the function and relation of Prx2 and NF-κB,the value of Edaravone,providing experienceal base for clinical heal.Methods: Ninety healthy female Wistar rats ,weighing 180-200g were divided randomly into five groups: normal control group(18 rats), EAE group(18 rats), dexamethasone(DXM) group(18 rats), low dose of edaravone group(18 rats) and high dose of edaravone group(18 rats). Then each groups were divided into three subgroups: 7 day group, 16 day group, 23 day group.All the experimental rats were immunized subcutaneously in the four footpads and back with emulsion 0.5ml(0.1ml every part), which including fresh guinea pig spinal cord homogenate (GPSCH) as antigen, emulsified with an equal volume of complete Freund's adjuvant (CFA) containing Mycobacterium tuberculosis 6mg/ml. Clinical signs of EAE were assessed a minimum of twice daily by two investigators. Scores were assigned on the basis of the following symptoms: 1, tail weakness; 2, tail weakness plus limb asthenia; 3, mild limb paralysis; 4, severe limb paralysis; 5, moribund/dead. EAE group, DXM group, low dose of edaravone group and high dose of edaravone group were injected intraperitoneal respectively NS 0.5ml/d, DXM 5mg·kg-1·d-1, edaravone 3mg·kg-1·d-1, edaravone 10mg·kg-1·d-1. These treatments were started on the first day of immunization and continued until the animal were executed, and EAE group left untreated. During the experiment, the mean maximal score of animals at different time point and the incidence of disease were observed as results.At the time for sacrificed,the procedure as follows:anesthesia with intraperitoneal injection,take out the issues of the brain,fix with 4% formalin ,embedd in paraffin,sectioned at 5μm thickness,stained with HE to assess lymphocyte infiltration and inflammation,immunol histochemistry to observe the amount of NF-κBand Prx2.Results:1 compare the morbidity of different group Morbidity of high dose of edaravone group and DXM group were significantly lower than those of EAE group (p <0.05).2 Observations the behavior of different group Neurological deficits scores of high dose of edaravone group and DXM group were significantly lower than those of EAE group (p<0.05).3 Observations NeuropathologicalThe results demonstrated that some monocytes infiltration was observed in the tissues of brains before the clinical signs emerging and the worse of the clinical sign,the more monocytes infiltration. The degree of infiltration was associated with the severity of EAE. The extent of inflammation of high dose of edaravone group and DXM group were significantly lower than those of EAE group (p <0.05).4 Observations the expression of NF-kB and Prx2The expression of NF-ΚB and Prx2 in brain in 16 day group of EAE group were higher than that of normal control group (p<0.05) and closely related to the action of EAE rats; The expression of NF-ΚB and Prx2 in the DXM group and high dose of edaravone group were lower than that of EAE group (p <0.05).Conclusions:1 The amount of NF-ΚB and Prx2 in brain correlated with the severity and activity of EAE. DXM and edaravone inhibit the oxidative stress,relive the dangerous of free radical,then the amount of NF-ΚB and Prx2 decline。2 Edaravone reduces the morbidityand the lymphocyte infiltration ,and protects the rats from the severity of the disease.3 Edaravone has good safty and tolerance compared with DXM. These results suggest that edaravone may be used in the demyelinating diseases like MS in the future.
|
PDF Full Text Request