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羚珠散对小鼠癫痫发作的预防作用及机制探讨
陆炜晟,王成稷,王海杰
0
(上海实验动物研究中心,上海,201203)
摘要:
目的:评价羚珠散治疗小鼠癫痫发作的预防作用及机制。方法:将25只C57BL/6小鼠随机分成3组,其中模型组和给药组每组各10只,正常组5只。采用腹腔注射戊四氮的方法制备癫痫模型,给药组每次造模前30 min灌胃羚珠散(剂量:1500 mg/kg)进行预防给药,每2 d重复一次造模和给药,共进行3次;正常组给予同体积0.9%氯化钠注射液。通过Racine评分评价造模后小鼠癫痫发作情况,于末次注射24h后分离各组小鼠大脑皮层和海马组织,通过Real-time PCR和免疫组化检测小鼠Gabbr1和Kcnt1基因蛋白表达情况。结果:Racine评分模型组显著高于正常组(P<0.0001),给药组显著低于模型组(P<0.0001);HE染色切片显示,药物作用后可以有效减少海马体组织细胞的损伤,与正常组接近;给药组海马组织中Gabbr1基因表达显著高于模型组(P=0.0335),但与正常组比较,差异无统计学意义(P>0.05);Kcnt1基因表达显著高于模型组(P=0.0139)与正常组(P=0.0063)。免疫组化结果显示,给药组中,小鼠海马组织Gabbr1和Kcnt1蛋白表达程度高于模型组(PGabbr1=0.0194,PKcnt1=0.0037)与正常组(PGabbr1=0.0094,PKcnt1=0.0255)。结论:羚珠散具有预防和抗小鼠癫痫的作用,其机制可能与钾离子通道KCNT1介导的抑制作用有关。
关键词:  癫痫  羚珠散  PTZ  Gabbr1  Kcnt1
DOI:
Preventative effect of Lingzhu powder against seizure in mice and its mechanism
LU Weisheng,WANG Chengji,WANG Haijie
(Shanghai Laboratory Animal Research Center,Shanghai 201203,China)
Abstract:
Objective:To investigate the preventative effect of Lingzhu powder against seizure in mice and its mechanism.Methods:A total of 25 C57BL/6 mice were randomly divided into model group with 10 mice,administration group with 10 mice,and normal group with 5 mice.Intraperitoneal injection of pentetrazol was performed to establish a model of epilepsy;the mice in the administration group were given Lingzhu powder (at a dose of 1500 mg/kg) for prophylaxis by gavage at 30 minutes before modeling,and modeling and administration were performed once every 2 days for 3 times in total;the mice in the normal group were given an equal volume of 0.9% sodium chloride injection.Racine score was used to evaluate seizure after modeling;cerebral cortex and hippocampal tissue were isolated at 24 hours after the last injection,and real-time PCR and immunohistochemistry were used to measure the mRNA and protein expression levels of Gabbr1 and Kcnt1 in mice.Results:The model group had a significantly higher Racine score than the normal group (P<0.0001),and the administration group had a significantly lower Racine score than the model group (P<0.0001).HE staining showed a significant reduction in cell injury in hippocampal tissue after administration,which was similar to the normal group.The administration group had a significantly higher mRNA expression level of Gabbr1 in hippocampal tissue than the model group (P=0.0335),with no significant difference between the administration group and the normal group (P>0.05),and the administration group had a significantly higher mRNA expression level of Kcnt1 than the model group and the normal group (P=0.0139 and 0.0063).Immunohistochemistry showed that compared with the model group and the normal group,the administration group had significantly higher protein expression levels of Gabbr1 and Kcnt1 in hippocampal tissue (Gabbr1:P=0.0194 and 0.0094;Kcnt1:P=0.0037 and 0.0255).Conclusion:Lingzhu powder can prevent and exert a therapeutic effect on epilepsy in mice possibly by the inhibitory role mediated by the potassium channel KCNT1.
Key words:  epilepsy  Lingzhu powder  pentetrazol  Gabbr1  Kcnt1

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