Tumor necrosis factor-α （TNF-α） plays a key role in the pathogenesis of experimental autoimmune neuritis （EAN） as well as Guillain-Barre syndrome. The proposed pathogenesis of TNF-α associated neuropathies invo...Tumor necrosis factor-α （TNF-α） plays a key role in the pathogenesis of experimental autoimmune neuritis （EAN） as well as Guillain-Barre syndrome. The proposed pathogenesis of TNF-α associated neuropathies involves immune-mediated attack to blood-nerve barrier, aggravated production of pro-inflammatory cytokines, and the induction of Schwann cells apoptosis. TNF-α may play a regulatory role by increasing production of interleukin-1 in macrophages, attenuating T cell receptor signaling and regulating apoptosis of potentially autoreactive T cells in EAN. The data suggest that antagonizing TNF-α functions or suppressing TNF-α production may be useful in the acute phase of EAN treatment, but further studies are required.展开更多
AIM：To determine whether gypenosides have protective effects in experimental autoimmune optic neuritis（EAON）.METHODS：Mice were randomly divided into seven groups：control group,model group,three different density ...AIM：To determine whether gypenosides have protective effects in experimental autoimmune optic neuritis（EAON）.METHODS：Mice were randomly divided into seven groups：control group,model group,three different density gypenosides monotherapy,methylprednisolone monotherapy,combination of gypenosides and methylprednisolone group.The control group was subcutaneously injected with oil emulsion adjuvant and all other groups were subcutaneously immunized with an emulsified mixture of myelin oligodendrocyte glycoprotein（MOG） 35-55 peptide to induce EAON.Mice in the gypenosides groups were administered injections daily with three concentrations（15 mg/kg,30 mg/kg,45 mg/kg） of gypenosides respectively.Mice in the methylprednisolone group and the combination treatment group were injected daily with methylprednisolone（20 mg/kg） or methylprednisolone（20 mg/kg） ＋ gypenosides（30 mg/kg）,respectively.After MOG immunization,visual evoked potential（VEP）,optical coherence tomography（OCT）,and histopathologic examination were performed at 14,20,30,and 40 d post-inoculation（p.i.）.All results were expressed as mean±SEM.The data were evaluated by oneway ANOVA followed by Tukey or Games-Howell test.RESULTS：Compared with the control group,p2 latency was prolonged in the model group（P=0.041）.Combination treatment can alleviated the change in VEP at 20 d p.i.（P=0.012）.Average peripapillary retinal nerve fiber layer（RNFL） thickness was reduced in the model group（P= 0.000,30d;P=0.000,40d） and gypenosides treatment remarkably diminished the degree of RNFL degenerationat 30 d and 40 d p.i（P=0.000,30d;P=0.000,40d）.The pathomorphological results showed a decrease in demyelination（P=0.020） and inflammatory reactions in the combination group compared with the model group（20d p.i.）.Gypenosides treatment also alleviated the degree of axonal loss（40d p.i.）（P=0.003）.CONCLUSION：Treatment with gypenosides exerts protective effects on retinal nerve fibers and axons in EAON.When combined with gypenosides,methylprednisolone reduces demyelination in the acute stage of EAON.展开更多
文摘Tumor necrosis factor-α （TNF-α） plays a key role in the pathogenesis of experimental autoimmune neuritis （EAN） as well as Guillain-Barre syndrome. The proposed pathogenesis of TNF-α associated neuropathies involves immune-mediated attack to blood-nerve barrier, aggravated production of pro-inflammatory cytokines, and the induction of Schwann cells apoptosis. TNF-α may play a regulatory role by increasing production of interleukin-1 in macrophages, attenuating T cell receptor signaling and regulating apoptosis of potentially autoreactive T cells in EAN. The data suggest that antagonizing TNF-α functions or suppressing TNF-α production may be useful in the acute phase of EAN treatment, but further studies are required.
基金Supported by the National Natural Science Foundation of China(No.81260149No.81360152No.81560162)
文摘AIM：To determine whether gypenosides have protective effects in experimental autoimmune optic neuritis（EAON）.METHODS：Mice were randomly divided into seven groups：control group,model group,three different density gypenosides monotherapy,methylprednisolone monotherapy,combination of gypenosides and methylprednisolone group.The control group was subcutaneously injected with oil emulsion adjuvant and all other groups were subcutaneously immunized with an emulsified mixture of myelin oligodendrocyte glycoprotein（MOG） 35-55 peptide to induce EAON.Mice in the gypenosides groups were administered injections daily with three concentrations（15 mg/kg,30 mg/kg,45 mg/kg） of gypenosides respectively.Mice in the methylprednisolone group and the combination treatment group were injected daily with methylprednisolone（20 mg/kg） or methylprednisolone（20 mg/kg） ＋ gypenosides（30 mg/kg）,respectively.After MOG immunization,visual evoked potential（VEP）,optical coherence tomography（OCT）,and histopathologic examination were performed at 14,20,30,and 40 d post-inoculation（p.i.）.All results were expressed as mean±SEM.The data were evaluated by oneway ANOVA followed by Tukey or Games-Howell test.RESULTS：Compared with the control group,p2 latency was prolonged in the model group（P=0.041）.Combination treatment can alleviated the change in VEP at 20 d p.i.（P=0.012）.Average peripapillary retinal nerve fiber layer（RNFL） thickness was reduced in the model group（P= 0.000,30d;P=0.000,40d） and gypenosides treatment remarkably diminished the degree of RNFL degenerationat 30 d and 40 d p.i（P=0.000,30d;P=0.000,40d）.The pathomorphological results showed a decrease in demyelination（P=0.020） and inflammatory reactions in the combination group compared with the model group（20d p.i.）.Gypenosides treatment also alleviated the degree of axonal loss（40d p.i.）（P=0.003）.CONCLUSION：Treatment with gypenosides exerts protective effects on retinal nerve fibers and axons in EAON.When combined with gypenosides,methylprednisolone reduces demyelination in the acute stage of EAON.
