维格列汀通过上调胰高血糖素样肽1发挥抗癫痫作用  

Vildagliptin suppresses temporal lobe epilepsy by up-regulating glucagon-like peptide-1

作　　者：温跃桃 吴昆仑[1] 石全红[1] 

机构地区：[1]重庆医科大学附属第一医院神经外科,重庆400016

出　　处：《南方医科大学学报》2017年第1期36-43,共8页Journal of Southern Medical University

基　　金：重庆市卫生局重点资助项目(2013-1-005)

摘　　要：目的探讨维格列汀对戊四氮(PTZ)诱导的癫痫模型中胰高血糖素样肽1(GLP-1)及胰高血糖素样肽1受体(GLP-1R)的影响而发挥抗癫痫作用。方法脑外伤患者切除的皮质为对照组(control;n=14),颞叶癫痫(TLE)患者行癫痫灶切除的皮质为颞叶癫痫组(n=23)。90只SD雄性大鼠随机分为对照组(A组,control)、PTZ单纯致痫组(B组,PTZ-induced epilepsy)、生理盐水2 m L/kg干预组(C组,PTZ+2 m L/kg saline)、维格列汀2.5 mg/kg干预组(D组,PTZ+2.5 mg/kg vildagliptin)、维格列汀5 mg/kg干预组(E组,PTZ+5 mg/kg vildagliptin)、维格列汀10 mg/kg干预组(F组,PTZ+10 mg/kg vildagliptin)。连续腹腔注射PTZ(35 mg/kg)3周建立慢性癫痫模型,观察大鼠行为学。运用Western blotting、免疫组织化学染色检测各组GLP-1R的表达变化,运用酶联免疫吸附检测各组血清中GLP-1的表达变化,采用免疫荧光染色和ELISA对GLP-1R进行定位。结果免疫荧光染色结果显示,GLP-1R主要表达于人体脑组织以及大鼠脑组织的神经元;免疫组织化学染色和Western blotting结果显示GLP-1R在癫痫患者以及癫痫模型中表达降低(P<0.05);在大鼠中,维格列汀可以有效的延长癫痫发作的潜伏期和降低癫痫发作次数;维格列汀干预后,GLP-1R的表达升高(P<0.05)。ELISA结果显示GLP-1与GLP-1R的表达变化一致(P<0.05)。结论维格列汀通过上调GLP-1和GLP-1R发挥抗癫痫作用。Objective To investigate the effect of vildagliptin on pentamethazol （PTZ）-induced epilepsy in rats and explore the molecular mechanism. Methods Samples of temporal cortex from 23 patients with temporal lobe epilepsy were collected as epilepsy group and samples of temporal cortex from 14 patients with brain trauma were used as control group. Ninety male SD rats were randomly divided into control group （group A）, PTZ-induced epilepsy group （group B）, saline 2 mL/kg group （group C）, vildagliptin 2.5 mg/kg group （group D）, vildagliptin 5mg/kg group （group D） and vildagliptin 10 mg/kg group （group F）. Use chronic model of epilepsy induced by PTZ （35 mg/kg） intraperitoneal injection for 3 consecutive weeks, and changes of behavior were observed. The expression of GLP-1R was detected by Western blotting and immunohistochemical （IHC） staining, and the expression of GLP-1 was detected by enzyme-linked immunosorbent assay （ELISA）. The location of GLP-1R was detected by immunofluorescent staining. Results Immunofluorescent staining showed that the GLP-1R located in the neurons, and GLP-1R expression was obviously decreased both in patients with TLE and in rats with epilepsy. The latency time was prolonged and epilepsy attack time was decreased after vildagliptin treatment （P〈0.05）. GLP-1R expression was increased after vildagliptin treatment （P〈0.05）. ELISA showed the change of GLP-1 expression was the same as GLP-1R. Conclusion Vildagliptin can suppress temporal lobe epilepsy in rats by up-regulating GLP-1 and GLP-1R expressions.

关 键 词：维格列汀 颞叶癫痫 胰高血糖素样肽1受体 胰高血糖素样肽1 glucagon-like peptide-1 

分 类 号：R742.1[医药卫生—神经病学与精神病学]