柴胡疏肝汤对慢性颞叶癫痫大鼠行为学及NMDA受体亚单位NR2B和CaMKⅡ蛋白表达的影响  

Effects of Chai-Hu Shu-Gan Decoction on Behavior and Protein Expressions of NMDA Receptor Subunits NR2B and CaMKⅡ of Chronic Temporal Lobe Epilepsy Rat Model

作　　者：金汉娜[1] 谢炜[1,2] 禤正正 洪雨[1] 周扬[1] 任志军[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：《世界科学技术-中医药现代化》2015年第12期2577-2583,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基委金面上项目(81373810):NMDAR"偶联"Kv4.2通道参与癫痫病理机制及"从肝论治"的干预作用;负责人:谢炜;广东省科技厅社会发展领域科技计划项目(2013A032500004):NMDAR"偶联"KV4.2通道参与癫痫病理机制及"从肝论治"的干预作用;负责人:谢炜

摘　　要：目的:研究柴胡疏肝汤对氯化锂-匹罗卡品所致的慢性颞叶癫痫模型大鼠NMDA(N-methylD-aspartate)受体亚单位NR2B和钙调蛋白依赖性蛋白激酶Ⅱ(Calcium/Calmodulin-dependent Protein KinaseⅡ,CaMKII)表达及行为学的影响。方法:将50只制备成功的Wistar慢性颞叶癫痫大鼠(B)随机分为5组(B_(1-5)),艾芬地尔组(B_2)予艾芬地尔(ifenprodil)10 mg·kg^(-1)腹腔注射,柴胡疏肝汤低、中、高剂量组(B_(3-5))分别予柴胡疏肝汤2.5,5,10 g·kg^(-1)灌胃,空白对照组(A)和生理盐水组(B_1)均予等容积生理盐水腹腔注射,各组连续干预8周,同时进行行为学视频监测,8周后运用免疫组织化学和western blot检测各组大鼠海马、颞叶皮层NR2B和CaMKII的表达情况。结果:艾芬地尔组和柴胡疏肝汤高剂量组大鼠的发作次数较模型组明显降低(P<0.05);在大鼠海马、颞叶皮层,与空白对照组相比,模型组NR2B和CaMKII的表达水平明显增高(P<0.05);与模型组相比,艾芬地尔组及柴胡疏肝汤高剂量组NR2B和CaMKII的表达水平降低(P<0.05);艾芬地尔组与柴胡疏肝汤高剂量组的表达无明显差异(P>0.05)。结论:柴胡疏肝汤高剂量可减少慢性颞叶癫痫大鼠痫性发作次数,且具有抑制NR2B及CaMKII的作用,这可能是柴胡疏肝汤发挥其抗癫痫作用的机制之一。This study was aimed to investigate the effects of Chai-Hu Shu-Gan decoction（CHSGD） on protein expressions of N-methyl-D-aspartate（NMDA） receptor subunits NR2 B and calcium/calmodulin-dependent protein kinase Ⅱ（CaMKII） as well as behavior among lithium chloride-pilocarpine induced chronic temporal lobe epilepsy（TLE） rat model.A total of 50 successfully established chronic TLE Wistar rats models（B） were randomly divided into 5 groups（B_1-5）.The ifenprodil group（B_2） was intraperitoneal injected with 10 mg·kg^（-1） of ifenprodil.In the low-,middle-,high-dose CHSGD group（B_3-5）,the intragastric administration of 2.5,5,and 10 g·kg^（-1） CHSGD was given,respectively.Intraperitoneal injection of equal volume normal saline was given to the blank control group（A）and the normal saline group（B_1）.The intervention was given for 8 weeks in each group.The video surveillance on behavior was recorded simultaneously.After 8 weeks,expressions of NR2 B and CaMKII in hippocampus and temporal lobe of rats in each group were detected by the immunohistochemical technique and western blot.As a result,the frequency of convulsion in the ifenprodil group and the high-dose CHSGD group was significantly reduced compared with the model group（P〈0.05）.Compared with the blank control group,the expression levels of NK2 B and CaMKII in hippocampus and temporal lobe of the model group were obviously increased（P〈0.05）.Compared with the model group,the expression levels of NR2 B and CaMKII in the ifenprodil group and the highdose CHSGD group were reduced（P〈0.05）.There was no significant difference on expressions between the ifenprodil group and the high-dose CHSGD group（P〉0.05）.It was concluded that high-dose CHSGD can reduce the frequency of convulsion in chronic TLE rats,inhibit NR2 B and CaMKII,which may be one of the possible mechanisms of antiepileptic effect for CHSGD.

关 键 词：慢性颞叶癫痫 柴胡疏肝汤 NR2B CAMKII 

分 类 号：R742.1[医药卫生—神经病学与精神病学]