柴胡疏肝汤对慢性颞叶癫痫大鼠海马Kv4.2及KChIP1通道蛋白表达的影响  

Effect of Chaihu Shugan Decoction on Potassium Channel Kv4.2 and Kv Channel Interacting Protein KCh IP1 in Adult Rats with Chronic Lobe Epilepsy

作　　者：禤正正 谢炜[1,2] 金汉娜[1] 洪雨[1] 周扬[1] 任志军[1] 胡冬蓉[1] 

机构地区：[1]南方医科大学中医药学院,广州510515 [2]南方医科大学南方医院,广州510515

出　　处：《中国实验方剂学杂志》2016年第12期113-117,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上基金项目(81373810);广东省科技厅社会发展领域科技计划项目(2013A032500004);高等学校博士学科点专项科研基金项目(201144331100)

摘　　要：目的:观察柴胡疏肝汤对匹罗卡品导致的慢性颞叶癫痫大鼠海马A型钾离子通道电压门控型钾通道4.2(Kv4.2)及钾离子通道相互作用蛋白1(KCh IP1)表达的影响。方法:SPF级Wistar大鼠80只,ip匹罗卡品,经过潜伏期后有自发发作即为成功模型,将成功模型随机分为模型组、钾通道开放剂瑞替加滨组、柴胡疏肝汤低、中、高剂量组,每组10只,另设正常组10只,分别给予瑞替加滨12.5 mg·kg^(^(-1))·d^(^(-1)),柴胡疏肝汤低、中、高剂量2.5,5,10 g·kg^(^(-1))·d^(^(-1)),正常组与模型组对应给予等体积生理盐水,连续干预8周,2次/d。通过视频录像监测系统观察各组癫痫发作次数的变化;通过免疫组化法、蛋白质免疫印迹(Western blot)检测各组大鼠海马Kv4.2通道蛋白和KCh IP1蛋白表达。结果:连续干预8周后,与模型组比较,瑞替加滨、柴胡疏肝汤低中、高剂量组大鼠癫痫发作次数均有不同程度的减少(P<0.05,P<0.01),而F组发作次数最少(P<0.01);与正常组比较,模型组海马区两蛋白的表达均明显降低(P<0.05),瑞替加滨、柴胡疏肝汤低中、高剂量组Kv4.2表达较模型组升高(P<0.05),其中瑞替加滨组与柴胡疏肝汤低高剂量组表达量相近。瑞替加滨、柴胡疏肝汤低高剂量组海马KCh IP1的表达也较模型组升高(P<0.05)。结论:柴胡疏肝汤中、高剂量能减少癫痫发作次数,其可能的机制是上调Kv4.2通道蛋白和KCh IP1蛋白表达。Objective： To investigate the effect of Chaihu Shugan decoction on the expression of voltagegated potassium channel 4. 2（ Kv4. 2） and Kv channel-interacting protein 1（ KCh IP1） in a rat model of chronic temporal lobe epilepsy induced by pilocarpine. Method： Totally 80 SPF Wistar rats were injected with pilocarpine intraperitoneally,and those with spontaneous recurrent seizures after latent period were selected into the model. All of the modeled rats were randomly divided into five groups： model group,potassium channel agonist retigabine treatment group（ 12. 5 mg·kg-1·d-1）,and high,medium and low-dose Chaihu Shugan decoction groups（ 2. 5,5,10 g·kg-1）,with 10 rats in each group. Another 10 normal rats were included in the normal group and administrated with saline same as model group. All groups were treated for 8 weeks. To evaluate the effect on seizure frequencies,the behavior of the rats were continuously recorded by digital camera during the study. The expression of the voltage-gatedpotass iumchannel 4. 2（ Kv4. 2） and KCh IP1 in hippocampus and temporal lobe were detected through immunohistochemistry and Western blot. Result： After 8 weeks of treatment,retigabine group and Chaihu Shugan decoction groups（ medium and high doses） showed significantly low seizure frequencies than model group（ P〈0. 05）. Compared with normal group,the expressions of the two proteins in model group reduced in hippocampus（ P〈0. 05）; retigabine group and Chaihu Shugan decoction group（ medium and high doses） showed remarkably higher Kv4. 2 expression（ P〈0. 05）,and retigabine group was similar with Chaihu Shugan decoction low and high-dose groups. Conclusion： Chaihu Shugan decoction had a significant effect on Kv4. 2 and KCh IP1 in CA1 region of hippocampus and temporal lobe in rats with chronic temporal lobe epilepsy.

关 键 词：柴胡疏肝汤 颞叶癫痫模型 电压门控型钾通道4.2 钾离子通道相互作用蛋白1 

分 类 号：R285.5[医药卫生—中药学]