摘要
[目的]通过观察疏风止痉方对耐药性癫痫大鼠脑组织NF-κB p65表达的影响及脑脊液卡马西平药物浓度的影响,探讨中药复方治疗难治性癫痫的作用机制。[方法]应用氯化锂-匹罗卡品点燃癫痫大鼠模型,将成功点燃的癫痫模型先后经过丙戊酸钠及卡马西平预处理后筛选出耐药性癫痫模型大鼠,将大鼠随机分为正常对照组、耐药模型组、阳性对照组、疏风止痉方低剂量组、疏风止痉方中剂量组、疏风止痉方高剂量组共6组,每组10只。灌胃治疗28 d后,采用免疫组化法和Western blot法检测海马NF-κB p65的分布表达,微透析技术联合高效液相色谱法采取并检测大鼠脑脊液的卡马西平浓度。[结果]除正常对照组外的其他各组脑脊液卡马西平浓度均高于耐药模型组,与阳性对照组比较差异有统计学意义(P<0.01);与阳性对照组比较,疏风止痉方各剂量组脑脊液卡马西平浓度虽均降低,但与疏风止痉方高剂量组比较无统计学差异;疏风止痉方各组随着中药剂量的增加,脑脊液中卡马西平浓度呈递增趋势,但3组之间无统计学差异。[结论]中药复方疏风止痉方联合卡马西平,通过调节耐药性癫痫大鼠脑内NF-κB炎症信号通路,抑制P-gp的过度表达,从而能够提高耐药性癫痫大鼠脑脊液中卡马西平的药物浓度,而且随着中药剂量的增加卡马西平浓度呈递增的趋势。
[Objective]To observe the effect of Shufeng Zhijing Recipe on the expression of NF-κB p65 in brain tissue of rats with druginduced epilepsy after lithium chloride-pilocarpine modeling and the extracellular fluid cerebrospinal fluid carbamazepine.The effect of concentration on whether the Chinese herbal compound Shufeng Zhijing Recipe can increase the expression of NF-κB p65 in the brain and the concentration of carbamazepine in the treatment of refractory epilepsy.[Method]Lithium chloride-pilocarpine was used to ignite the rat model of epilepsy.The successfully ignited epilepsy model was screened by sodium valproate and carbamazepine,and the drugresistant epilepsy model rats were screened.The drug-resistant epilepsy rats were randomly divided into normal control group,drug resistance model group,positive control group,Shufeng Zhijing Recipe low-dose group,Shufeng Zhijing Recipe group,Shufeng Zhijing Recipe high-dose group.There were 6 groups,10 in each group.After 28 days of intragastric administration,the expression of NF-κB p65 in hippocampus was detected by immunohistochemistry and Western blot.The concentration of carbamazepine in rat brain extracellular cerebrospinal fluid was determined by microdialysis technique combined with high performance liquid chromatography.[Results]Compared with the drug resistance model group,the concentration of carbamazepine in the cerebrospinal fluid of all groups except the normal control group was higher than that in the drug resistance model group,but only significantly different from the positive control group(P<0.01).Compared with the positive control group,the concentration of carbamazepine in the cerebrospinal fluid of each dose group of Shufeng Zhijing Recipe decreased,but there was no significant difference between the high-dose group and Shufeng Zhijing Recipe.The concentration of carbamazepine in the cerebrospinal fluid increased with the increase of the amount of the drug in the group,but there was no significant difference between the three groups.[Conclusion]Ch
作者
戎萍
闫融
马茗晗
张喜莲
马融
RONG Ping;YAN Rong;MA Minghan;ZHANG Xilian;MA Rong(Paediatrics Department,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China)
出处
《天津中医药》
CAS
2019年第11期1116-1120,共5页
Tianjin Journal of Traditional Chinese Medicine
基金
国家自然科学基金青年项目(81503612)
关键词
癫痫
耐药性
疏风止痉方
卡马西平
脑脊液
epilepsy
drug resistance
Shufeng Zhijing Recipe
carbamazepine
cerebrospinal fluid
