耐抗癫痫药大鼠模型脑内P-糖蛋白的表达

目的：通过耐丙戊酸钠（VPA）、耐卡马西平（CBZ）大鼠惊厥模型探讨癫痫耐药机制。方法：采用大鼠腹腔注射戊四氮（PTz）21d的点燃方法，建立大鼠惊厥模型。在此基础上分别以CBZ及VPA灌胃14d，建立耐CBZ及耐VPA大鼠惊厥模型。实验分4组：正常对照组、惊厥对照组、耐CBZ组及耐VPA组，每组8只鼠。以惊厥潜伏期和Racine行为学分级作为评定药效指标。采用免疫组化法检测大鼠脑内P-糖蛋白（Pgp）的表达变化；统计分析各组大鼠脑内Pgp表达量，探索癫痫大鼠的耐药机制。结果：①24只大鼠在连续腹腔注射PTZ21d达点燃标准，成功建立惊厥模型；②取16只惊厥大鼠分两组各灌胃CBZ及VPA14d后，两组大鼠惊厥潜伏期（5．84士2．94和6．23土2．57min）较惊厥对照组的惊厥潜伏期（3．32±1．83min）显著延长（P〈0．01），提示耐CBZ及耐VPA模型制备成功；③惊厥对照组PgP的表达（12．40±10．35）比正常对照组（1．62±0．85）增高，差异有统计学意义（P〈0．01）；耐CBZ组（38．67±17．28）及耐VPA组大鼠的PgP的表达（42．33±15．54）较惊厥对照组（12．40±10．35）增高，差异有显著意义（P〈0．01）；而耐CBZ组与耐VPA组之间PgP的差别则无统计学意义（P〉O．05）。结论：①大鼠腹腔注射PTz21d，建立惊厥模型，再进一步分别灌胃CBZ及VPA14d，成功建立耐CBZ及耐VPA模型；②CBZ和VPA可显著诱导Pgp的表达，而长期惊厥发作对其表达也可能有一定的诱导Pgp表达的作用。

The Pgp expresion in the brain of CBZ- and VPA-resistant rat models

Objective：To explore the drug-resistant function mechanism by observing pglycoprotein （Pgp） expression in carbamazepine（CBZ）-resistant and valproate（VPA）-resistant rat models induced by enterocelia injection of pentetrazole（PTZ）. Methods：The convulsive rat models were made by enterocelia injection of PTZ in rats for 21 days,then stomach filling by CBZ and VPA were performed in convulsive model rats for 14 days to establish the VPA-resistant and CBZ-resistant convulsive rat models respetive- ly. Four groups in the study include the normal control group, the convulsive model group, CBZ-resistant group and VPA-resistant group,with grats each. Latency of convulsion and Racine＇s behavior classifica- tion serve as indicators. Immunohisto-chemistry was adopted to determine the changes of Pgp expression. Results：O24 rats appeared convulsive symptom after injection of PTZ for 21 days. The rats convulsive model was established successfullyQstomch filling by CBZ or VPA was performed respectively in con- vulsive model rats for 14 days,the convulsant latency（5.84± 2.94） mini or （6.23± 2.57） mini of CBZ-resistant or VPA-resistant rats significantly increased as compared with the convulsire model rats（3.32± 1.83 min）（P〈0.01）. The CBZ-resistant and VPA-resistant rat models were established suceessfullyl （1）Pgp expressre increased in the convulsive model control group（12.40 ± 10.35）than in normal control group （1.62±0.85）（P〈0.01） Pgp CBZ-resistant group（38.67±17. 28）and VPA-resistant group（42.33± 15.54）significantly increased than in the convulsive contral group（P〈0.01）. VPA-resistant model group had mord but fewer or Pgp expressions than CBZ-resistant models group（P〈0.05）. Conclusion ： （1） On the 21st day of low-dose PTZ irliection, the convulsive model can be established, and thetl filling stomch re- spectively by CBZ and VPA for 14 days, so as to setup the drug-resistant rat models;（2）CBZ and VPA can obviously induce the expressions of Pgp which is also influenced by long convulsion.