氟西汀治疗实验性自身免疫性脑脊髓炎的作用

目的 初步探讨盐酸氟西汀对实验性自身免疫性脑脊髓炎(EAE)大鼠的干预作用和发病过程中不同时间点血清脑源性神经营养因子(BDNF)的表达.方法 将Wistar大鼠随机分为3组:溶媒对照组(n=6)、模型对照组(n=10)和氟西汀组(10mg/kg,n=10);采用自制豚鼠脊髓匀浆足垫注射免疫动物制作EAE模型,每天观察各组大鼠神经功能缺损评分;采用双抗夹心酶联免疫吸附试验(ELISA)分别检测大鼠免疫前、免疫后第16天及免疫后第25天血清BDNF的表达.结果 1、模型对照组及氟西汀组大鼠在免疫后第4天开始出现毛发无光泽及脱毛,在免疫后第8天开始出现鼠尾下垂,并逐渐发展至不同程度的肢体无力,在免疫后第16天动物发病达到高峰;溶媒对照组大鼠无发病.2、氟西汀显著促进了大鼠神经功能恢复,在免疫后第18天开始氟西汀组[(3.27±0.33)分]与模型对照组[(4.66±0.55)分]的临床神经功能缺损评分开始出现显著性差异(P＜0.05),并持续至实验结束.3、氟西汀组与模型对照组大鼠相比血清中BDNF的表达差异无显著性[氟西汀组(62.27±0.43)ng/L;模型对照组(61.67±0.85)ng/L,P＞0.05].结论 氟西汀显著促进了EAE大鼠的神经功能恢复,提示其具有治疗EAE动物的作用;氟西汀并不能通过促进EAE大鼠血清中BDNF的表达参与保护作用.

Abstract：

Objective To investigate whether fluoxetine has therapeutic effect of clinical score and brain derived neurotrophic factor (BDNF) expression in serum of experimental autoimmune encephalomyelitis (EAE)model. Methods Rats were randomly divided into solvent control group (n=6) ,model control group ( n= 10)and fluoxetine group ( n= 10). The EAE model was prepared by injecting guinea pig spinal cord homogenate subcutaneously. The clinical score was daily measured according to the sign and symptoms of rats in the behavior examination. The serum BDNF level was measured by EL1SA. Results 1. Except for the solvent control group,the first sign of EAE(Piloerection) was detected on 4th day after immunization of rats from both model control group and fluoxetine group,then EAE rats had distal tail weakness on 8th day, and gradually developed into completely tail paralysis and limb paralysis. EAE rats' clinical score reached the peak on 16th day after immunization. 2. The clinical score of fluoxetine group became scientifically lower than model group since 18th day after immunization ( Fluoxetine group :3.27 ± 0. 33; Model control group :4.66 ± 0. 55, P ＜ 0. 05 ). 3. Compared with the model control group,fluoxetine did not significantly increase the expression of serum BDNF in EAE model ( Fluoxetine group:62.27 ± 0.43; Model control group :61.67 ± 0.85, P ＞ 0.05 ). Conclusion Fluoxetine reduced the clinical score of EAE since 18th day after immunization,which indicates fluoxetine could promote the recovery of neurological function in EAE rats. BDNF may not contribute to protective effect of fluoxetine in EAE animal.

The therapeutic effects of fluoxetine on experimental autoimmune encephalomylitis

Objective To investigate whether fluoxetine has therapeutic effect of clinical score and brain derived neurotrophic factor (BDNF) expression in serum of experimental autoimmune encephalomyelitis (EAE)model. Methods Rats were randomly divided into solvent control group (n=6) ,model control group ( n= 10)and fluoxetine group ( n= 10). The EAE model was prepared by injecting guinea pig spinal cord homogenate subcutaneously. The clinical score was daily measured according to the sign and symptoms of rats in the behavior examination. The serum BDNF level was measured by EL1SA. Results 1. Except for the solvent control group,the first sign of EAE(Piloerection) was detected on 4th day after immunization of rats from both model control group and fluoxetine group,then EAE rats had distal tail weakness on 8th day, and gradually developed into completely tail paralysis and limb paralysis. EAE rats' clinical score reached the peak on 16th day after immunization. 2. The clinical score of fluoxetine group became scientifically lower than model group since 18th day after immunization ( Fluoxetine group :3.27 ± 0. 33; Model control group :4.66 ± 0. 55, P ＜ 0. 05 ). 3. Compared with the model control group,fluoxetine did not significantly increase the expression of serum BDNF in EAE model ( Fluoxetine group:62.27 ± 0.43; Model control group :61.67 ± 0.85, P ＞ 0.05 ). Conclusion Fluoxetine reduced the clinical score of EAE since 18th day after immunization,which indicates fluoxetine could promote the recovery of neurological function in EAE rats. BDNF may not contribute to protective effect of fluoxetine in EAE animal.