OBJECTIVE:To examine the effects of catalpol and rhein on pro-and anti-inflammatory responses in C57 BL/6 mice with experimental autoimmune encephalomyelitis(EAE),a model of multiple sclerosis.METHODS:Female C57 BL/6 ...OBJECTIVE:To examine the effects of catalpol and rhein on pro-and anti-inflammatory responses in C57 BL/6 mice with experimental autoimmune encephalomyelitis(EAE),a model of multiple sclerosis.METHODS:Female C57 BL/6 mice were randomly divided into four groups(n=30):(a)normal salinecontrol,(b)EAE control,(c)EAE+prednisone acetate(PA,6 mg/kg),and(d)EAE+catalpol(40 mg/kg)and rhein(5 mg/kg).EAE was induced by injection of myelin oligodendrocyte glycoprotein 35-55 plus pertussis toxin.Treatments were orally administered daily for 40 d.Disease progression and neurological function were assessed using a semi-quantitative scale of tail and limb paralysis.Brains and spinal cords were collected on Days 6,20,and 40 and assessed for histopathological changes by hematoxylin and eosin staining.Production of interleukin(IL)-2,IL-4,IL-10,and IL-17 A protein was measured by enzyme-linked immunosorbent assay.Expression of the T helper(Th)1-,Th2-,Th17-,and regulatory T cell(Treg)-specific transcription factors T-bet,GATA3,ROR-γt,and Foxp3,respectively,were analyzed by quantitative reverse-transcription polymerase chain reaction and western blot analysis.RESULTS:Combination treatment with catalpol and rhein significantly alleviated the clinical disability and neurological dysfunction of mice with EAE.Catalpol and rhein treatment also reduced the infiltration of pro-inflammatory T cells into pathological lesions;significantly increased the expression of the anti-inflammatory factors GATA3,Foxp3,IL-4,and IL-10;and significantly decreased the expression of the pro-inflammatory factors T-bet,ROR-γt,IL-2,and IL-17 A.CONCLUSION:Catalpol and rhein reduced the neurological disabilities of mice with EAE,at least in part by rebalancing the pro-and anti-inflammatory environment in the brains and spinal cords.展开更多
OBJECTIVE:To investigate the changes of subcortical gray matter volume and cortical thickness,andexplorethe correlations between regional abnormalities of cortical thickness and cognitive impairment and the effect of ...OBJECTIVE:To investigate the changes of subcortical gray matter volume and cortical thickness,andexplorethe correlations between regional abnormalities of cortical thickness and cognitive impairment and the effect of modified Bushenyisui decoction(补肾益髓汤,BSYSD)on the cognitive function of multiple sclerosis(MS).METHODS:This prospective study was approved by the institutional review board.92 subjects were recruited,including 46 relapsing-remitting multiple sclerosis(RRMS)patients and 46 healthy controls(HC).Of the 46 patients,22 patients experienced the treatment of BSYSD for half a year.A conventional three-dimensional T1-weighted sequence were acquired for all participants on a 3.0 tesla magnetic resonance system.Basic information,detailed cognitive scales Montreal Cognitive Assessment(MoCA),symbol digit modalities test(SDMT),immediate memory,delayed recall,and long-term recognition were evaluated.Subcortical gray matter volume and cortical thickness weremeasured by FreeSurfer.The correlations between cortical thickness which MS patients showed reduced with respect to HC and cognitive scales wereanalyzed by Pearson correlation in RRMS patients.The influence of modified BSYSD on MS patients'cognition was analyzed by paired T Test.RESULTS:MoCA,immediate memory,delayed recall,and long-term delayed recognition in RRMS were significantly decreased than those of HC.Gray matter atrophy measured by FreeSurfer showed mainly in thalamus and hippocampus of RRMS patients.Compared with HC,the cortical thickness of several regions in frontal lobe,parietal lobe,temporal lobe,hippocampal,cingulate gyrus,and fusiform gyrus of RRMS patients were decreased with significant difference.The regions of cortical thickness thinning related to MoCA,immediate memory,delayed recall,and long-term delayed recognition were temporal lobe and fusiform gyrus.Modified BSYSD could improve MoCA,SDMT,immediate memory,delayed recall,and long-term delayed recognition of MS patients,and it could promote the recovery of cognitive function in MS patients.CONCLUSIONS:Gray matter atrophy and cortical thickness thinning were validated in RRMS.Cortical thickness thinning of temporal lobe and fusiform gyrus strongly related to cognitive deficits in RRMS.The modified BSYSD could promote the recovery of cognitive function in MS.展开更多
基金Supported by the National Natural Science Foundation(No.81973599)Beijing Natural Science Foundation-Key Project of Science and Technology Plan of Beijing Education Commission(KZ/KM/SZ/SM201910025035)The Fund for Beijing Science&Technology Development of Traditional Chinese Medicine(No.QN2018-30)
文摘OBJECTIVE:To examine the effects of catalpol and rhein on pro-and anti-inflammatory responses in C57 BL/6 mice with experimental autoimmune encephalomyelitis(EAE),a model of multiple sclerosis.METHODS:Female C57 BL/6 mice were randomly divided into four groups(n=30):(a)normal salinecontrol,(b)EAE control,(c)EAE+prednisone acetate(PA,6 mg/kg),and(d)EAE+catalpol(40 mg/kg)and rhein(5 mg/kg).EAE was induced by injection of myelin oligodendrocyte glycoprotein 35-55 plus pertussis toxin.Treatments were orally administered daily for 40 d.Disease progression and neurological function were assessed using a semi-quantitative scale of tail and limb paralysis.Brains and spinal cords were collected on Days 6,20,and 40 and assessed for histopathological changes by hematoxylin and eosin staining.Production of interleukin(IL)-2,IL-4,IL-10,and IL-17 A protein was measured by enzyme-linked immunosorbent assay.Expression of the T helper(Th)1-,Th2-,Th17-,and regulatory T cell(Treg)-specific transcription factors T-bet,GATA3,ROR-γt,and Foxp3,respectively,were analyzed by quantitative reverse-transcription polymerase chain reaction and western blot analysis.RESULTS:Combination treatment with catalpol and rhein significantly alleviated the clinical disability and neurological dysfunction of mice with EAE.Catalpol and rhein treatment also reduced the infiltration of pro-inflammatory T cells into pathological lesions;significantly increased the expression of the anti-inflammatory factors GATA3,Foxp3,IL-4,and IL-10;and significantly decreased the expression of the pro-inflammatory factors T-bet,ROR-γt,IL-2,and IL-17 A.CONCLUSION:Catalpol and rhein reduced the neurological disabilities of mice with EAE,at least in part by rebalancing the pro-and anti-inflammatory environment in the brains and spinal cords.
基金Supported by the Fund for BeijingScience&Technology Development of TCM:the Study on the Curative Effect and Mechanism of Modification of Bushenyisui Capsules against Multiple Sclerosis with Depression Based on Magnetic Resonance Multimodal Analysis(No.JJ2018-49)the Effect of Bushenyisui Capsules on Cognitive Impairment in Patients with Relapsing and Multiple Sclerosis(No.QN2014-17)+4 种基金To Explore the Mechanism of Bushenyisui Capsule in Reconstituting NMOSD Immune Balance Based on the Regulation of p38 MAPK Pathway by TAK1(No.QN2018-30)Capital Medical University Scientific Research Cultivation Fund:Rl Promotes the Recovery of Neurological Function in Rats with Cerebral Hemorrhage through the Pathway of Microglial Cells Polarizing Different Neurons to Mediate the Neuroinflammatory Reaction after Cerebral Hemorrhage(No.PYZ2018142)to Explore the Mechanism of Bushenyisui Capsule Promoting Myelin Sheath Regeneration in EAE Mice by Regulating Proliferation,Differentiation and Migration of OPC by Treg Derived Nov(No.PYZ2018141)National Natural Science Foundation of China:to Explore the Mechanism of Catalpol Mediated Proliferation,Migration and Axonal Remyelination of OPC by CCN3 through the Synergetic Regulation of Cdc42 Signaling Pathway by GEFs and mir-148b-3p(No.81973599)the Study on the Mechanism of Regulating the Axon Myelination through NF and NRG1(No.81473640)。
文摘OBJECTIVE:To investigate the changes of subcortical gray matter volume and cortical thickness,andexplorethe correlations between regional abnormalities of cortical thickness and cognitive impairment and the effect of modified Bushenyisui decoction(补肾益髓汤,BSYSD)on the cognitive function of multiple sclerosis(MS).METHODS:This prospective study was approved by the institutional review board.92 subjects were recruited,including 46 relapsing-remitting multiple sclerosis(RRMS)patients and 46 healthy controls(HC).Of the 46 patients,22 patients experienced the treatment of BSYSD for half a year.A conventional three-dimensional T1-weighted sequence were acquired for all participants on a 3.0 tesla magnetic resonance system.Basic information,detailed cognitive scales Montreal Cognitive Assessment(MoCA),symbol digit modalities test(SDMT),immediate memory,delayed recall,and long-term recognition were evaluated.Subcortical gray matter volume and cortical thickness weremeasured by FreeSurfer.The correlations between cortical thickness which MS patients showed reduced with respect to HC and cognitive scales wereanalyzed by Pearson correlation in RRMS patients.The influence of modified BSYSD on MS patients'cognition was analyzed by paired T Test.RESULTS:MoCA,immediate memory,delayed recall,and long-term delayed recognition in RRMS were significantly decreased than those of HC.Gray matter atrophy measured by FreeSurfer showed mainly in thalamus and hippocampus of RRMS patients.Compared with HC,the cortical thickness of several regions in frontal lobe,parietal lobe,temporal lobe,hippocampal,cingulate gyrus,and fusiform gyrus of RRMS patients were decreased with significant difference.The regions of cortical thickness thinning related to MoCA,immediate memory,delayed recall,and long-term delayed recognition were temporal lobe and fusiform gyrus.Modified BSYSD could improve MoCA,SDMT,immediate memory,delayed recall,and long-term delayed recognition of MS patients,and it could promote the recovery of cognitive function in MS patients.CONCLUSIONS:Gray matter atrophy and cortical thickness thinning were validated in RRMS.Cortical thickness thinning of temporal lobe and fusiform gyrus strongly related to cognitive deficits in RRMS.The modified BSYSD could promote the recovery of cognitive function in MS.
