熄风胶囊对匹罗卡品IE大鼠血液及脑细胞外液卡马西平药物浓度影响的实验研究  

Effect of Xifeng Capsule on the Concentration of Carbamazepine in Blood and Brain Extracellular Fluid in Epileptic Rats

作　　者：吴超[1] 李新民[2] 张喜莲[2] 路岩莉[2] 房艳艳[1] 聂坤[2] 刘菁[2] 

机构地区：[1]天津中医药大学,天津300193 [2]天津中医药大学第一附属医院,天津300193

出　　处：《中医药学报》2018年第1期48-53,共6页Acta Chinese Medicine and Pharmacology

基　　金：国家自然科学基金资助项目(81373690)

摘　　要：目的:通过观察熄风胶囊对氯化锂-匹罗卡品造模后的癫痫大鼠血液和脑细胞外液卡马西平药物浓度的影响,来判断其是否能够增加血脑屏障的通透性。方法:应用氯化锂-匹罗卡品诱导难治性癫痫大鼠模型,将造模成功的癫痫大鼠随机分为卡马西平组、熄风胶囊加卡马西平组(熄卡组)、熄风胶囊加卡马西平1/2剂量组(熄卡低组)、熄风胶囊高剂量组(熄高组)、熄风胶囊中剂量组(熄中组)、熄风胶囊低剂量组(熄低组)、模型对照组(模型组)及空白对照组(空白组)共8组,每组12只。灌胃治疗2个月后,从卡马西平组、熄卡组、熄卡低组中各取6只大鼠,采用脑微透析技术联合高效液相色谱法按不同时间点取样并检测大鼠血液及脑细胞外液的卡马西平的药物浓度。结果:(1)与卡马西平组相比,熄卡组中卡马西平的血药浓度在各个时间点略有升高,但无统计学意义;熄卡组中卡马西平的脑药浓度在各时间点同样有所升高(在30~90 min,P<0.05)。(2)与熄卡组相比,熄卡低组的卡马西平的血药及脑药浓度在各个时间点虽均降低,但高于熄卡组中卡马西平浓度的一半(在15~90 min,P<0.05)。(3)卡马西平浓度的脑血比:卡马西平组:0.055∶1;熄卡组:0.072∶1;熄卡低组:0.073∶1。结论:熄风胶囊可能会升高卡马西平在脑细胞外液及血液中的药物浓度,增强血脑屏障的透过作用;对于低剂量的卡马西平可能更加敏感,能够降低卡马西平用量,从而减少其副作用及不良反应。Objective: To observe the effect of Xifeng capsule on the concentration of Carbamazepine(CBZ) in blood and brain extracellular fluid in epileptic rats triggered by aluminium chloride and Pilocapine,to determine whether it could increase the permeability of blood-brain barrier. Methods: Rats were randomly divided into the blank control group(group A,n = 12),the model group(group B,n = 12),CBZ group(group C,n = 12),Xifeng capsule and CBZ group(group D,n = 12),Xifeng capsule and 1/2 CBZ group(group E,n = 12),high-dose Xifeng capsule group(group F,n = 12),medium-dose Xifeng capsule group(group G,n = 12),and low-dose Xifeng capsule group(groupH,n =12). Epilepsy models were established with Aluminium Choloride and Pilocapine. Every six rats from group C,group D,and group E were tested CBZ concentration in blood and brain extracellular fluid at different time points with microdialysis and HPLC techniques. Results: In comparison with group C,the blood concentration of CBZ in group D was slightly higher than that in group C at each time point,but there was no statistical significance; CBZ concentration in brain extracellular fluid in group D was also increased(30-90 min,P < 0. 05). CBZ concentrations in blood and brain extracellular fluid were reduced in group E at different time point compared to group D,which were higher than half concentration of CBZ in group D(15-90 min,P < 0. 05). In terms of CBZ ratio of cerebral and blood it was 0. 055: 1 in group C,0. 072: 1 in group D,and 0. 073: 1 in group E. Conclusion: Xifeng capsule may increase CBZ concentration in blood and brain extracellular fluid,reinforce the permeablility of blood brain barrier; it can reduce the dose of CBZ,cut down CBZ's adverse reaction.

关 键 词：熄风胶囊 卡马西平 血脑屏障 微透析 高效液相色谱法 

分 类 号：R742.1[医药卫生—神经病学与精神病学]