头孢曲松对抑郁模型C57小鼠行为及海马谷氨酸转运体1蛋白表达的影响

Effects of ceftriaxone on depressive-like behavior and changes of hippocampal glutamate transporter-1 in depression model C57 mice

目的 探讨头孢曲松对抑郁模型C57小鼠行为及海马谷氨酸转运体1蛋白表达（glutamate transporter-1,GLT-1）的影响,进一步探讨头孢曲松抗抑郁作用可能的分子机制.方法 将30只雄性C57小鼠随机分为对照组（A组）、CUS组（B组）、CUS＋头孢曲松组（C组）各10只.CUS组、CUS＋头孢曲松组进行连续21 d,2次/d的CUS应激、随后给予CUS＋头孢曲松组小鼠头孢曲松21 d的治疗,对照组和CUS组给予生理盐水.观察小鼠应激前、应激后及头孢曲松治疗后糖水偏好和旷场行为的变化,同时在行为学测试结束后使用免疫印迹分析检测3组小鼠海马G LT-1蛋白的表达水平.结果 （1）行为学测试结果显示,应激21 d后CUS组和CUS＋头孢曲松组小鼠糖水偏好,总行程,平均移动速度及直立次数与对照组相比显著下降（P＜0.05）;CUS＋头孢曲松组小鼠经头孢曲松治疗21 d后糖水偏好（78.74±3.54）％,总行程（6818.35±505.14） cm,平均移动速度（12.36±0.89） cm/s,直立次数（58.20±4.05）次,与CUS组[（59.46±2.75）％、（2931.71±271.89） cm、（5.84±0.42） cm/s、（26.20±2.62）次]比较有明显改善（R0.05）.（2）免疫印迹分析显示,CUS组与对照组比较,小鼠海马GLT-1蛋白表达下降（P＜0.05）,经头孢曲松治疗后,小鼠海马GLT-1蛋白表达比CUS组明显升高（P＜0.05）.结论 头孢曲松对CUS小鼠的抑郁样行为有明显改善作用;慢性应激（CUS）下调小鼠海马GLT-1蛋白表达水平,而头孢曲松上调GLT-1蛋白表达水平,GLT-1蛋白表达增加可能是头孢曲松抗抑郁作用的分子机制.

Objective To investigate the effects of ceftriaxone on depressive-like behavior and changes of hippocampal glutamate transporter-1 （GLT-1） in C57 mice depression model,and to further explore the molecular mechanism of ceftriaxone on antidepressant action.Methods Thirty male C57 mice were randomly divided into control group（group A,n=10）,CUS group（group B,n=10） and CUS＋ceftriaxone group（group C,n=10）.The mice of the CUS group and the CUS＋ceftriaxone group were subjected to chronic unpredictable stress （CUS） for 2 sessions per day for 21 days.Then,the mice of the CUS＋ceftriaxone group were given ceftriaxone for 21 days.Behavioral changes were assessed by the sucrose preference test and open field test.The GLT-1 protein levels in the hippocampus were detected by Western blot analysis at the end of the ceftriaxone treatment.Results （1） Compared with the control group,the percentage of sucrose preference,the total traveled distance,the moved velocity,and the frequencies of rearing of the CUS group were significantly decreased（P＜0.05） at the 21 days.However,the percentage of sucrose preference （（78.74 ± 3.54） ％）,the total traveled distance （（6818.35 ± 505.14） cm）,the moved velocity（（12.36±0.89） cm/s）,and the frequencies of rearing（58.20±4.05） of the CUS＋ceftriaxone group at the end of the ceftriaxone treatment were improved significantly compared with the CUS group （（59.46 ± 2.75） ％,（2931.71±271.89） cm,（5.84±0.42） cm/s,（26.20±2.62）,P＜0.05）.（2） Western blot analysis indicated significant reductions of the GLT-1 protein levels in the hippocampus of CUS group （versus the control mice：P ＜0.05）,and chronic ceftriaxone treatment reversed the CUS-induced decrease in the GLT-1 levels（P＜0.05）.Conclusion Ceftriaxone might significantly improve depressive-like behavior in C57 mice depression model.Chronic unpredictable stress （CUS） could down-regulate the GLT-1 protein levels in the hippocampus,which are reversed by ceftriaxone.These results further support the notion enhanced expression of the GLT-1 protcin can be molecular mechanism of ceftriaxone on antidepressant action.