Wen Yue-Tao, Wu Kun-Lun, Shi Quan-Hong
Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2017 Jan 20;37(1):36-43. doi: 10.3969/j.issn.1673-4254.2017.01.07.
To investigate the effect of vildagliptin on pentamethazol (PTZ)-induced epilepsy in rats and explore the molecular mechanism.
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.
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.
Vildagliptin can suppress temporal lobe epilepsy in rats by up-regulating GLP-1 and GLP-1R expressions.
探讨维格列汀对戊四氮(PTZ)诱导的大鼠癫痫的影响并探究其分子机制。
收集23例颞叶癫痫患者的颞叶皮质样本作为癫痫组,选取14例脑外伤患者的颞叶皮质样本作为对照组。将90只雄性SD大鼠随机分为对照组(A组)、PTZ诱导癫痫组(B组)、生理盐水2 mL/kg组(C组)、维格列汀2.5 mg/kg组(D组)、维格列汀5mg/kg组(E组)和维格列汀10 mg/kg组(F组)。采用腹腔注射PTZ(35 mg/kg)连续3周诱导慢性癫痫模型,观察行为变化。通过蛋白质免疫印迹法和免疫组织化学(IHC)染色检测GLP-1R的表达,采用酶联免疫吸附测定(ELISA)检测GLP-1的表达。通过免疫荧光染色检测GLP-1R的定位。
免疫荧光染色显示GLP-1R位于神经元中,颞叶癫痫患者和癫痫大鼠的GLP-1R表达均明显降低。维格列汀治疗后潜伏期延长,癫痫发作时间缩短(P<0.05)。维格列汀治疗后GLP-1R表达增加(P<0.05)。ELISA显示GLP-1表达变化与GLP-1R相同。
维格列汀可通过上调GLP-1和GLP-1R的表达抑制大鼠颞叶癫痫。