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
文摘目的:目前阿加曲班在急性缺血性卒中(acute ischemic stroke,AIS)中的疗效和安全性尚存在争议,临床应用仍存在较大分歧。本文将针对阿加曲班治疗AIS的疗效和安全性展开系统性评价及Meta分析。方法:计算机检索通过PubMed、The Cochrane library、Embase、ClinicalTrials.gov、中国知网(China National Knowledge Infrastructure,CNKI)、中国生物医学文献数据库(China Biology Medicine disc,CBM)、维普网及万方数据知识服务平台收集应用阿加曲班治疗AIS的全部文献,检索的设定时间截至2022年4月。由2名受过培训的研究人员对文献进行筛选、数据提取和偏倚风险评估。采用RevMan 5.4软件对数据进行Meta分析。结果:共有25篇文献纳入本次Meta分析,共包含AIS患者4696例(其中阿加曲班组2271例,对照组2425例)。Meta分析结果显示:阿加曲班能促进AIS患者早期神经功能改善(OR=2.69,95%CI=1.66~4.34,P<0.001),减少早期神经功能恶化(OR=0.42,95%CI=0.29~0.60,P<0.001),但对于90 d改良Rankin量表(modified Rankin scale,mRS)评分0~1分患者比例(P=0.080)、90 d mRS评分0~2分患者比例(P=0.230)及卒中复发率(P=0.190)均无明显影响;亚组分析结果显示,阿加曲班联合口服抗血小板药物能改善90 d mRS评发0~2的患者比例,差异具有统计学意义(OR=1.55,95%CI=1.17~2.05,P=0.003);在安全性方面,阿加曲班及对照组在任何颅内出血(P=0.730)、症状性颅内出血(P=0.990)、系统性出血(P=0.150)及死亡率(P=0.990)上均无统计学差异。结论:阿加曲班可改善AIS患者早期神经功能预后,且不增加患者的出血风险及死亡率。
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.
