奥卡西平对红藻氨酸点燃发育期慢性癫痫大鼠海马多药耐药相关蛋白1表达的影响  

Effect of Oxcarbazepine on multidrug resistance associated protein 1 expression in hippocampus of kainic acid- induced seizure in rats during development period rats

作　　者：张亚楠[1] 戴园园[1] 李蕊[1] 孙明霞[1] 程华[1] 

机构地区：[1]徐州医学院附属医院儿科,221000

出　　处：《中华实用儿科临床杂志》2013年第15期1170-1173,共4页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的建立发育期慢性癫痫大鼠模型，观察海马区多药耐药相关蛋白1（MRP1）的表达，并探讨奥卡西平（OXC）对其表达的影响。方法将健康的14dSD大鼠100只随机分为模型组（n=52）和对照组（n=48），模型组予以腹腔注射红藻氨酸（KA）1mg／kg（质量浓度0．5g／L）建立慢性癫痫模型，注射后连续观察8h，按照Lado癫痫行为分级，癫痫发作达5级以上并出现癫痫持续状态的大鼠，且2周后出现自发性反复惊厥发作者视为造模成功；而对照组仅腹腔注射相同剂量的9g／L盐水。将造模成功后存活的48只大鼠随机分为KA组24只，KA＋OXC组24只，对照组48只大鼠随机分为Ns组、Ns＋OXC组各24只，其中均于癫痫自发性反复发作后开始用药，根据其疗程不同分为第4周组、第6周组、第8周组，然后将所有大鼠灌注取脑，用免疫组织化学法测定大鼠海马CA3区MRP1的表达。结果1．大鼠行为学：Ns组及Ns＋OXC组大鼠无痫性发作，进入慢性期后，KA组、KA＋OXC各组大鼠均出现自发性痫性发作，但KA＋OXC组发作频率较KA组明显降低（P〈0．05）。2．NS组、Ns＋OXC组大鼠海马CA3区仅有少量MRP1阳性细胞表达，二者比较差异无统计学意义（P〉0．05）；随着观察时间的延长，KA组MRP1阳性细胞渐升高，与Ns组比较各时间点差异均有统计学意义（P〈0．05）；KA＋OXC组MRP1免疫组织化学法阳性细胞与KA组有类似趋势，2组比较在第4周、第6周表达量差异均无统计学意义（P均〉0．05）；而在第8周时MRP1表达量明显增高，差异有统计学意义（P〈0．05）；各时间点KA＋OXC组与Ns＋OXC组MRP1表达量差异均有统计学意义（P均〈0．05）。结论MRP1参与慢性癫痫耐药的发生，OXC长期干预治疗可能诱导大鼠MRP1的表达。Objective To observe the expressions of muhidrug resistance-associated protein （MRP）1 in the hippocampus of the rat models with chronic epilepsy, and to explore whether antiepileptic drug oxcarbazepine（OXC） af- fects the expression of MRPt. Methods One hundred rats of 14 days old were randomly divided into model group（ n = 52） and the control group （ n = 48 ）. The model group received intraperitoneal injection of kainic acid （KA） 1 mg/kg （0.5 g/L） to induce seizures,and the control group rats were injected the same dose of 9 g/L chloride. According to Lado standard classification of seizures, the young rats whose seizure degree was beyond 5 and became status epilepticus after intraperitoneal injection used as successful seizure models if they caught the spontaneous seizures after 2 weeks. When spontaneous seizures were developed,48 surviving KA rats were divided into KA group and KA ＋ OXC group. Rats in the control group were divided into NS group and NS ＋ OXC group. After spontaneous recurrent seizures, the treatment groups began to take drugs. Each group started to be sacrificed from the beginning of drug perfusion at diffe- rent times and they were divided into the 4th week group, the 6th week group and the 8th week group. The expression of MRP1 in hippocampus（ CA3 area） was detected by immunohistochemistry methods. Results 1. Epileptic performance ： all rats injected with NS had no epileptic performance. In the chronic epilepsy, I -V Racine grade of spontaneous re- current seizures were found in all rats with KA. The rats in KA group had higher epilepsy seizure frequency than those in KA ＋ OXC group（P 〈0.05）. 2. The rats in NS group and NS ＋ OXC group had fewer MRP1 positive cells,and there was no significant difference at all time points between NS group and NS ＋ OXC group （P 〉 0.05 ）. The trend of expres- sion in KA group and KA ＋ OXC group gradually increased. The MRP1 positive cells in KA ＋ OXC group compared with those in the KA group was significan

关 键 词：奥卡西平 多药耐药相关蛋白 慢性癫痫 

分 类 号：R742.1[医药卫生—神经病学与精神病学]