OBJECIVE:To investigate the efficacy and mechanisms of Dingxian pill(定痫丸)combined with valproic acid(VPA)on pentylenetetrazol-induced chronical epilepsy in rats.METHODS:A rat model of epilepsy was established by ad...OBJECIVE:To investigate the efficacy and mechanisms of Dingxian pill(定痫丸)combined with valproic acid(VPA)on pentylenetetrazol-induced chronical epilepsy in rats.METHODS:A rat model of epilepsy was established by administering pentylenetetrazol(PTZ)water solution(35 mg/kg).Rats were divided into 4 groups,among which three groups were treated with different drugs once a day for 28 d including Dingxian pill(2.4 g/kg),VPA(0.2 g/kg),or a combination of Dingxian pill(2.4 g/kg)and VPA(0.2 g/kg)respectively,and the control group was given the same volume of saline.Rats in different groups were compared based on animal behavior,electroencephalograms,Morris water maze,immunohistochemistry,transcriptomics and real-time polymerase chain reaction.RSULTS:The combination therapy of Dingxian pill and VPA inhibited PTZ-induced seizure-like behavior and reduced seizure grades more significantly than VPA alone.Compared with the control group,the learning and memory ability of chronic PTZ-induced epileptic rats was improved in all the drug treatment groups,especially in the group that received both Dingxian pill and VPA.Similar to the results of MWM tests,expression of the neuroexcitability marker gene c-Fos was reduced after Dingxian pill and/or VPA treatment,and the effect was most pronounced in the combined treatment group.Transcriptomic analysis revealed that gene expression in the rodent hippocampus,which is involved in epilepsy,was upregulated by combined treatment with Dingxian pill and VPA,compared with VPA treatment alone.CONCLUSION:Our results not only highlight the antiepileptic effects of combined Dingxian pill and VPA treatment,but also shed light on the underlying molecular mechanisms and provide a way to apply Traditional Chinese Medicine in the treatment of epilepsy.展开更多
基金Supported by National Natural Science Foundation of China:Molecular Mechanism Underlying the Intervention of Scorpion Extract BmK IT2 on Epileptogenesis via Voltage-gated Nav1.6 Channels in Hippocampal Neurons(No.81903995)Molecular Mechanism Underlying the Intervention of Scorpion Polypeptide MarTX on Temporal Lobe Epileptogenesis by Inhibiting Mechanosensitive Channel Piezo1(No.82074162)+5 种基金Youth Talent Promotion Project of China Association of Chinese Medicine(No.CACM-2019-QNRC2-C10)Project for Capacity Promotion of Putuo District Clinical Special Disease(Stroke,2019tszb02)Science and Technology Innovation Project of Putuo District Health System:Molecular Mechanism of Aerobic Exercise Intervention on Post-epileptic Depression Through"Bone-brain Axis"(No.ptkwws202107)the Antiepileptic Mechanism of Scorpion Active Extract BmK AS Regulating Nav1.6 Sodium Channel in Hippocampal Pyramidal Neurons(No.ptkwws201902)Evaluation of Microglial Lysosomal BK Channels as Molecular Targets for Clinical Treatment of Temporal Lobe Epilepsy(ptkwws201908)Molecular Mechanism of Sodium Channel SCN8A(Nav1.6)Mutation Mediating Epilepsy and Sodium Valproate Resistance in Children the Research Project of Putuo Hospital,Shanghai University of Traditional Chinese Medicine(No.2019308),(No.2019307)。
文摘OBJECIVE:To investigate the efficacy and mechanisms of Dingxian pill(定痫丸)combined with valproic acid(VPA)on pentylenetetrazol-induced chronical epilepsy in rats.METHODS:A rat model of epilepsy was established by administering pentylenetetrazol(PTZ)water solution(35 mg/kg).Rats were divided into 4 groups,among which three groups were treated with different drugs once a day for 28 d including Dingxian pill(2.4 g/kg),VPA(0.2 g/kg),or a combination of Dingxian pill(2.4 g/kg)and VPA(0.2 g/kg)respectively,and the control group was given the same volume of saline.Rats in different groups were compared based on animal behavior,electroencephalograms,Morris water maze,immunohistochemistry,transcriptomics and real-time polymerase chain reaction.RSULTS:The combination therapy of Dingxian pill and VPA inhibited PTZ-induced seizure-like behavior and reduced seizure grades more significantly than VPA alone.Compared with the control group,the learning and memory ability of chronic PTZ-induced epileptic rats was improved in all the drug treatment groups,especially in the group that received both Dingxian pill and VPA.Similar to the results of MWM tests,expression of the neuroexcitability marker gene c-Fos was reduced after Dingxian pill and/or VPA treatment,and the effect was most pronounced in the combined treatment group.Transcriptomic analysis revealed that gene expression in the rodent hippocampus,which is involved in epilepsy,was upregulated by combined treatment with Dingxian pill and VPA,compared with VPA treatment alone.CONCLUSION:Our results not only highlight the antiepileptic effects of combined Dingxian pill and VPA treatment,but also shed light on the underlying molecular mechanisms and provide a way to apply Traditional Chinese Medicine in the treatment of epilepsy.
文摘目的探讨定痫方加减联合奥卡西平治疗血液透析相关性癫痫(Hemodialysis-associated seizure,HAS)肾虚痰瘀证的临床疗效。方法选取2019年1月—2021年12月期间石家庄市中医院收治的HAS患者34例,按随机数字表法分为对照组和观察组,每组各17例。对照组口服奥卡西平片,观察组在对照组基础上加服定痫方加减治疗。治疗3个月后,观察比较两组患者临床疗效,治疗前后中医证候积分、血清神经元特异性烯醇化酶(Neuron-specific enolase,NSE)、胶质纤维酸性蛋白(Glial fibrillary acidic protein,GFAP)、S100钙结合蛋白B(S100 calcium-binding protein B,S100B)及炎性因子[肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白介素-1β(Interleukin-1β,IL-1β)、环氧化酶-2(Cyclooxygenase-2,COX-2)及高迁移率族蛋白B1(High mobility group protein B1,HMGB1)]水平,记录两组患者治疗前后癫痫发作持续时间和发作频次。结果治疗后观察组总有效率94.12%(16/17)高于对照组82.35%(14/17),差异有统计学意义(P<0.05)。治疗后两组患者各项证候积分和总积分均较治疗前降低,差异有统计学意义(P<0.05);且观察组各项证候积分和总积分均低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者癫痫发作持续时间和发作频次均较治疗前降低,差异有统计学意义(P<0.05);且观察组癫痫发作持续时间和发作频次低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清NSE、GFAP和S100B水平均较治疗前降低,差异有统计学意义(P<0.05);且观察组NSE、GFAP和S100B水平均低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清TNF-α、IL-1β、COX-2及HMGB1水平均较治疗前降低,差异有统计学意义(P<0.05);且观察组TNF-α、IL-1β、COX-2及HMGB1水平均低于对照组,差异有统计学意义(P<0.05)。治疗期间两组患者均未见明显的药物不良反应。结论定痫方加减联合奥卡西平治疗HAS肾虚痰瘀证的临床疗效显著且安全,可减轻血脑屏障破坏和神经元损伤程度,改善患者癫痫症状,其机制可能与抑制脑内炎症反应有关。
