头孢曲松对甲基苯丙胺致大鼠伏隔核神经元和谷氨酸转运体改变的影响

摘要

目的 观察头孢曲松对甲基苯丙胺(METH)急性、亚急性处理时致神经损伤情况的影响,以及对伏隔核中谷氨酸转运体1(GLT1)与囊泡型谷氨酸转运体1(VGLUT1)的变化的影响.方法 建立METH急性毒性模型,同时利用谷氨酸转运体调节剂头孢曲松调控谷氨酸转运体的表达,尼氏染色实验观测神经元中尼氏小体的变化,利用Western blot实验检测其谷氨酸转运体蛋白表达的变化.结果 METH急性给药组与盐水对照组相比,刻板行为明显增加(P<0.01),尼氏小体明显减少;伏隔核中GLT1和VGLUT1的表达增加分别为53.7%和102%(P<0.05);头孢曲松预防给药组与METH组相比,大鼠刻板行为明显减少,伏隔核中GLT1的表达增加36%(P<0.05);VGLUT1的表达下调56%(P<0.05);METH亚急性处理后,与盐水对照组相比,伏隔核中GLT1的蛋白表达增加40.9%,VGLUT1蛋白表达增加52.9%;预防给予头孢曲松后,头孢曲松预防给药组与METH组相比,GLT1和VGLUT1蛋白表达差异没有显著性.结论 METH处理导致神经损伤,引起伏隔核中谷氨酸转运体的表达变化;头孢曲松能激活谷氨酸转运体的表达,缓解METH引起的神经损伤.%Aim To observe the role of ceftrixone on neuro-injury induced by methamphetamine( METH )a-cute/sub-acute treatment, and changes of glutamate transporter l( GLT1 )and vesicular glutamate transport- ( Cef )was applied to regulate the expression of gluta-mate transporters. The neurotoxicity of METH was e-valuated by Nissl staining method and stereotyped behavior. The expression of GLT1 protein and VGLUT1 protein was evaluated by Western blot. Results Compared to the saline group, stereotyped behaviors in METH acute-treated group significantly increased, and the density of nissl significantly reduced; the expression of GLT1 protein and VGLUT1 protein in METH group was significantly up-ragulated by 53. 7% and 102% ( P <0. 05 )in nucleus accumbens; compared to the METH group, pre-administration of ceftriaxone sodium with METH decreased stereotyped behaviors, GLT1 protein expression was also siginificantly in- er l( VGLUT1 )in nucleus accumbens under different conditions. Methods Rats were administered ( ip ) with METH to establish acute and sub-acute toxicity model , and the glutamate transporter agonist ceftriaxone creased by 36% , and VGLUT1 protein expression was down-regulated by 56% ( P < 0. 05 ). Compared to the saline group, the expression of GLT1 and VGLUT1 in nucleus accumbens of rats which sub-acuted treated by METH increased by 40. 9% and 52. 9% , and there was no significant diffierence in pre-administration of ceftriaxone sodium group and METH sub-acuted group. Conclusions Acute sub-acute administration of METH can cause nerve injury and dysregulation of glu-tamate transporters in striatum; ceftriaxone which can regulate expression of glutamate transports can dilute nerve injury induced by METH.