卡马西平对癫痫大鼠中脑腹侧被盖区多巴胺能神经元Kv7.4通道的影响  

Effects of carbamazepine on Kv7.4 channel of VTA dopaminergic neurons in epileptic rats

作　　者：王大永 裴剑 洪铭岩[2] 徐翔 高云鹤 郑宇 王凯杰[2] 崔建忠[2] Wang Da-Yong;Pei Jian;Hong Ming-Yan;Xu Xiang;Gao Yun-He;Zheng Yu;Wang Kai-Jie;Cui Jian-Zhong(Department of Neurointerventional Therapy,Tangshan Workers'Hospital,Tangshan,Hebei 063000,China;Department of Neurosurgery,Tangshan Workers'Hospital,Tangshan,Hebei 063000,China)

机构地区：[1]唐山市工人医院神经介入科,河北唐山063000 [2]唐山市工人医院神经外科,河北唐山063000

出　　处：《解放军医学杂志》2023年第8期887-892,共6页Medical Journal of Chinese People's Liberation Army

基　　金：河北省科技厅国际合作课题资助项目(20397747D)。

摘　　要：目的观察卡马西平(CBZ)对癫痫大鼠中脑腹侧被盖区(VTA)多巴胺(DA)能神经元Kv7.4通道的影响。方法50只雄性Wistar大鼠随机分为5组:对照组、癫痫组和低、中、高浓度CBZ组,每组10只。对照组以外的4组大鼠均用氯化锂-匹罗卡品诱发癫痫构建癫痫大鼠模型;模型构建成功后,低、中、高浓度CBZ组分别通过灌胃给予10、30、50 mg/kg CBZ,对照组和癫痫组灌胃给予等量生理盐水,1次/d,连续7 d。观察各组大鼠行为学表现,通过分光光度法检测VTA丙二醛(MDA)、还原型谷胱甘肽(GSH)含量及超氧化物岐化酶(SOD)活性,免疫荧光及激光共聚焦观察各组大鼠VTA区酪氨酸羟化酶(TH)、Kv7.4蛋白的表达,Western blotting检测TH、Kv7.4的表达情况。结果对照组大鼠行为无异常;匹罗卡品注射后癫痫组大鼠出现抽搐、咀嚼、流涎等症状,低、中、高浓度CBZ组大鼠上述症状均有所缓解。与对照组比较,癫痫组大鼠VTA区MDA含量明显升高(P<0.05),GSH含量、SOD活性、DA能神经元数及TH、Kv7.4蛋白表达水平明显降低(P<0.05);与癫痫组大鼠比较,低、中、高浓度CBZ组大鼠癫痫发作潜伏期延长,VTA区GSH含量、SOD活性、DA能神经元数及TH、Kv7.4蛋白表达水平均明显升高(P<0.05),中、高浓度CBZ组大鼠癫痫发作率、VTA区MDA含量均明显降低(P<0.05)。结论CBZ可能通过抑制癫痫大鼠脑内氧化应激反应,促进VTA区DA能神经元活动,激活Kv7.4通道,缓解癫痫发作。Objective To investigate the effect of carbamazepine(CBZ)on Kv7.4 channels of dopaminergic(DA)neurons in the ventral tegmental area(VTA)of the midbrain of epileptic rats.Methods 50 male Wistar rats were randomly divided into 5 groups:control group,epilepsy group,and low,medium,high concentration CBZ group,10 in each group.Except control group,rats in other groups were induced epilepsy with lithium chloride and pilocarpine to establish epilepsy rat model.After the model was successfully constructed,the rats in low,medium,and high concentration CBZ groups were given CBZ(10,30,and 50 mg/kg)by gavage respectively,while rats in control group and epilepsy group were given the same amount of normal saline by gavage once a day for 7 days.The behavior changes of rats were observed.The malondialdehyde(MDA),glutathione(GSH)content and superoxide dismutase(SOD)activity in VTA were determinate by spectrophotometric.The protein expression of tyrosine hydroxylase(TH)and kv7.4 in VTA were detected by immunofluorescence and laser confocal microscopy.Western blotting was used to detecte the TH and Kv7.4 expression.Results No abnormal behavior showed with rats in control group.After pilocarpine injection,rats in epilepsy group experienced symptoms such as convulsions,chewing,and salivation,and the symptoms in low,medium,and high concentration CBZ group were alleviated.Compared with rats in control group,the MDA content of the rats in epilepsy group was significantly increased(P<0.05),the GSH content,SOD activity,number of DA neurons in the VTA region,and the expression of TH and Kv7.4 protein were significantly reduced(P<0.05).Compared with rats in epilepsy group,the seizure latency,GSH content,SOD activity,number of DA neurons in VTA area,and TH and Kv7.4 protein expression levels significantly increased in the low,medium and high concentration CBZ group(P<0.05);seizure rate and MDA content significantly decreased in the medium and high concentration CBZ group(P<0.05).Conclusions CBZ could alleviate oxidative stress response in br

关 键 词：卡马西平 癫痫 中脑腹侧被盖区 多巴胺能神经元 Kv7.4通道 

分 类 号：R742.1[医药卫生—神经病学与精神病学]