| Objective:Multiple sclerosis (MS) is an inflammatory demyelination andautoimmune disease of the central nervous system (CNS). Characterizedby recurrent and multifocal demyelination.Accompany withinflammatory cells infiltration,neuraxial degeneration,glial cellshyperplasia and progressive neurological impairment.It clinical courseassume relapsing-remitting,ladder sample development of neurologicalimpairmentand high morbidity.in recent years,people on the pathogenesisof multiple sclerosis did a lot of research, but the exact causes andmechanisms unknown. At present more scholars think could be due togenetic susceptibility to individual under the influence of the environmentfactors,causing the body start the abnormal autoimmune responses,thusresult in inflammatory myelin sheath loss of the central nervous system.Both CD4+and CD8+T lymphocytes cells mediated immunitymechanism play an important role in the pathogenesis of MS. Recentstudy found that inflammatory reaction and oxidative stress is also playa key role in the happened and development process of the MS.Oxidativestress and excited poison is common pathways of neurodegenerative. Thelevels of oxidation kinase in the cerebrospinal fluid and plasma of the MSpatients can all significantly increased.Experimental autoimmune encephalomyelitis(EAE),is recognized asa very vivid rodent model of human multiple sclerosis. It can beinduced in susceptible animals by immunization with myelinoligodendrocyte glycoprotein (MOG), myelin basic protein (MBP) ormyelin proteolipid protein (PLP),Because EAE shares many pathogenesis and histopathological features with multiple sclerosis(MS),it is usedacommonly as a ideal tool in the multiple sclerosis research.In our study we aims to establish an EAE model by MOG35-55inC57BL/6mice and to observe the effect of sulforaphane on incidencerate,neurobehavioral scores,organization pathological changes and theexpression of IL-23and NQO1proteins in the brain and spinal cord ofmice with experimentalautoimmune encephalomyelitis(EAE),To exploreif sulforaphane can play a protective effect o on EAE by raised Nrf2pathways and comparis the curative on sulforaphane and dexamethasone.It can make a theoretical and experimental basis for the further study ofthe pathogenesis, pathology and treatment of MS.Methods:female C57BL/6mice wheighted18-20g were induced byMOG35-55to make EAE model. They were randomly divided into ahealthy control group, EAE group,SFN group and DXM group.The miceof SFN and DXM group were injected sulforaphane(50mg/kg) anddexamethasone (0.07mg/kg·d) tertian,control and EAE groups wereinjected physiological saline (0.5ml/kg·d) tertian,from the immunizationto the day mice were saerifieed.Compare the incidence andneurobehavioral scores of mice in different time points, HistologicalExaminations were Performed on the sections of brain and spinal cordwith the aid of hematoxylin-eosin and Luxol Fast Bluemyelinstaining.The expressions of NQO1in brain tissue were detected by usingimmunohistochemistry technique and Western blot. The expressions ofIL-23in the peak of splenic lymphocytes were detected by ELISA.Results:1Pathogenesis of different groups;1.1The morbidity of SFN group (33.3%) and DXM group (27.8%) wassignificantly lower than EAE group's(100%)(P <0.05);1.2The mean time to develop disease for immune mice of EAE group,SFN group and DXMgroup respectively is(14.42±4.12)d; (16.78±3.11) d and(17.60±4.98)d, SFN group and DXM group wassignificantly later than EAE group's(P <0.05);1.3The mean weight fot the mice of control group,EAE group,SFNgroup and DXM group is respectively is (20.99±1.5),(18.42±2.69),(20.64±1.51)and (20.71±1.48); control group,SFN group andDXM group was significantly lower than EAE group's (P <0.05)；1.4The mean neurobehavioral scores at different time points for themice of control group,EAE group,SFN group and DXMgrouprespectively is(0.00±0.00)(,2.38±0.52)(,1.33±0.50)(,1.25±0.50);SFN group and DXM group was significantly lower than EAE group's(P <0.05)；2Histopathology of different groups in brain and spinal cordsHematoxylin-eosion (HE) and Luxol Fast Bluemyelinstaining(LFB)Staining histoPathology Results indicate that there was no inflammatorycell,"blood vessel muff",demyelination in the white matter or injuryof axon on sections of control group;the degree of inflammatory cellinfiltrating and myelin damage was heaviest in the peak for the mice ofEAE group,SFN group and DXM group,there are a lot of "blood vesselmuff" in the meantime; at different time points,the degree ofinflammatory cell infiltrating and myelin damager and the number of"blood vessel muff"for the mice of SFN group and DXM weresignificantly lower than EAE group's(P <0.05),while the SFN groupand DXM group there was no significantly statistical difference(p＞0.05).3The expression of NQO1in brain and spinal cord:3.1The results of immunohistochemical show that the mean numberof NQO1immunopositive cells in EAE group, SFN group and DXMgroup at different time point was all significantly increased than controlgroup's(P <0.05),and that of SFN group and DXM group wassignificantly more than EAE group's(P <0.05),SFN group wassignificantly more than DXM group's (P <0.05)3.2The results of Western blot show that the density relative value of NQO1/β-actin in EAE group, SFN group and DXM at different timepoints was all significantly higher than control group's(P <0.05),and thatof SFN group and DXM group was significantly higher than EAEgroup's(P <0.05), SFN group than DXM group was significantly higher(P <0.05)4The expression of IL-23in splenic lymphocytes: The results of ELISAshow that the concentration of IL-23in EAE group, SFN group andDXM at peak was significantly higher than control group's(P <0.05),and that of SFN group and DXM group was significantly lowerthan EAE group's(P <0.05),while SFN group and DXM group there wasno significantly statistical difference(p＞0.05).Conclusion:sulforaphane could lower the morbidity of EAE, delay the time ofpathogenesis,reduce the nerve damage of disease causing and alleviatethe degree of inflammatory cell infiltrating and myelin damager in brainand spinal cord tissue;it has a protective effect for the mouse of EAE.sulforaphane can upregulate the expression of NQO1in the brainand spinal cord tissue and has the function of downing antioxidant stress.sulforaphane can suppress the expression of IL-23in spleniclymphocytes and has the function of anti-inflammatory effect.sulforaphane's neuroprotective effect for the mouse of EAE may bethrough upregulation of Nrf2,playing the role of anti-inflammatory effectand antioxidant stress. |
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