目的 观察环氧化酶-2选择性抑制剂塞来昔布对癫癎持续状态大鼠脑内主穹隆蛋白(MVP)表达的影响,探讨其在治疗难治性癫癎中的作用及可能机制,为难治性癫癎的新药治疗提供理论依据。方法 健康成年雄性Sprague-Dawley大鼠60只,随机分为空白对照组(n=16)、癫癎模型组(n=22)和塞来昔布干预组(n=22),氯化锂-匹鲁卡品诱发大鼠癫癎持续状态模型成功后,各组均有16只大鼠纳入实验。采用免疫组化法和Westernblot法检测各组大鼠额叶皮质区及海马区MVP的表达情况。结果 癫癎模型组大鼠脑内MVP的表达水平较空白对照组显著增高(P<0.01);塞来昔布干预后的大鼠脑组织中MVP表达水平较癫癎模型组显著下降,但仍高于空白对照组(P<0.01)。结论 塞来昔布可降低MVP在癫癎持续状态大鼠脑组织中的高表达,有望为治疗难治性癫癎提供新方法 。
Abstract
Objective To study the effect of cyclooxygenase -2 selective inhibitor celecoxib on the expression of major vault protein ( MVP) in the brain of rats with status epilepticus and its possible roles in the treatment of refractory epilepsy. Methods Sixty adult male Sprague-Dawley rats were randomly assigned to blank control (n=16), epilepsy model (n=22) and celecoxib treatment groups (n=22). After the status epilepticus was induced in rats by injecting lithium and pilocarpine, each group had 16 rats enrolled as subjects. Immunohistochemical method and Western blot method were used to detect the expression of MVP in the frontal cortex and hippocampus. Results The expression of MVP was significantly higher in the epilepsy model group than in the control group (P<0.01). The expression of MVP in the celecoxib treatment group was significantly decreased compared with the epilepsy model group, but it was still higher than in the control group (P<0.01). Conclusions Celecoxib could decrease the expression of MVP in brain tissue of rats with status epilepticus, suggesting that it is promising for the treatment of intractable epilepsy.
关键词
塞来昔布 /
癫癎持续状态 /
主穹窿蛋白 /
大鼠
Key words
Celecoxib /
Status epilepticus /
Major vault protein /
Rats
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] 张刚. 小儿难治性癫癎的外科治疗及术前评估[J]. 儿科药学杂志, 2010, 16(4): 58-60.
[2] Vezzani A, Aronica E, Mazarati A, et al. Epilepsy and brain inflammation[J]. Exp Neurol, 2013, 244: 11-21.
[3] Schlichtiger J, Pekcec A, Bartmann H, et al. Celecoxib treatment restores pharmacosensitivity in a rat model of pharmacoresistant epilepsy[J]. Br J Pharmacol, 2010, 160(5): 1062-1071.
[4] 王海燕, 任艳霞, 杜宁. 海人酸致痫大鼠中多药耐药相关蛋白1 和主穹窿蛋白的表达及作用[J]. 黑龙江医药科学, 2011, 34(3): 1-2.
[5] Sun Q, Li Y. The inhibitory effect of pseudolaric acid B on gastric cancer and multidrug resistance via Cox-2/PKC-α/P-gp pathway[J]. PLoS One, 2014, 9(9): e107830.
[6] 李丹, 黄绍平, 马伟军, 等. 氯化锂-匹鲁卡品癫癎动物模型的建立[J]. 陕西医学杂志, 2006, 35(1): 15-17.
[7] Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure[J]. Electroencephalogr Clin Neurophysiol, 1972, 32(3): 281-294.
[8] Liu B, Wang T, Wang L, et al. Up-regulation of major vault protein in the frontal cortex of patients with intractable frontal lobe epilepsy[J]. J Neurol Sci, 2011, 308(1-2): 88-93.
[9] Balan S, Radhab SK, Sathyan S, et al. Major vault protein (MVP) gene polymorphisms and drug resistance in mesial temporal lobe epilepsy with hippocampal sclerosis[J]. Gene, 2013, 526(2): 449-453.
[10] Kedersha NL, Rome LH. Isolation and characterization of a novel ribonucleoprotein particle: large structures contain a single species of small RNA[J]. J Cell Biol, 1986, 103(3): 699-709.
[11] Gotovdorj T, Lee E, Lim Y, et al. 2,3,7,8-Tetrachlorodibenzop-dioxin induced cell-specific drug transporters with acquired cisplatin resistance in cisplatin sensitive cancer cells[J]. J Korean Med Sci, 2014, 29(9): 1188-1198.
[12] 郭效东, 刘备, 张华, 等. 难治性癫癎患者脑组织穹隆体主蛋白表达的研究[J]. 临床神经病学杂志, 2013, 26(3): 161-164.
[13] Rojas A, Jiang J, Ganesh T, et al. Cyclooxygenase-2 in epilepsy[J]. Epilepsia, 2014, 55(1): 17-25.
[14] Auvin S, Shin D, Mazarati A, et al. Inflammation induced by LPS enhances epileptogenesis in immature rat and may be partially reversed by IL1RA[J]. Epilepsia, 2010, 51 Suppl 3: 34-38.
[15] van Vliet EA, Zibell GA, Schlichtiger J, et al. COX-2 inhibition controls P-glycoprotein expression and promotes brain delivery of phenytoin in chronic epileptic rats[J]. Neuropharmacology, 2010, 58(2): 404-412.
[16] Citraro R, Leo A, Marra R, et al. Antiepileptogenic effects of the selective COX-2 inhibitor etoricoxib, on the development of spontaneous absence seizures in WAG/Rij rats[J]. Brain Res Bull, 2015, 113: 1-7.
[17] Annamaria V. Anti-inflammatory drugs in epilepsy: does it impact epileptogenesis? [J]. Expert Opin Drug Saf, 2015, 14(4): 583-592.
[18] 王宁, 秦明照. 选择性环氧化酶-2 抑制剂与心血管事件风险[J]. 心血管病学进展, 2013, 34(2): 170-173.
[19] Polascheck N, Bankstahl M, Löscher W. The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy[J]. Exp Neurol, 2010, 224(1): 219-233.
基金
2012年西安交通大学第二附属医院科研基金青年资助项目[YJ(QN)201213]。
PDF(1902 KB)
