【摘要】 目的观察柴胡皂苷A(SSA)对创伤性脑损伤大鼠认知功能及海马组织内cAMP/CREB信号通路及其调控的脑源性神经生长因子(BDNF)表达的影响。方法成年雄性SD大鼠60只,体重360~400g,随机分为假手术组(S组)、创伤组(T组)和创伤加SSA组(A组)。创伤后每天腹腔注射5mg/kg SSA(A组)或等容量生理盐水(S组、T组),连续5d。于创伤后1、3、7、14d,采用Morris水迷宫检测大鼠潜伏期和游泳距离;末次行为学测试后处死大鼠,采用ELISA法测定海马组织中BDNF和cAMP浓度,采用Western blot检测环磷酸腺苷反应元件结合蛋白(CREB)和磷酸化的环磷酸腺苷反应元件结合蛋白(pCREB)浓度。结果创伤后1、3、7、14dT组和创伤后1、3dA组大鼠潜伏期和游泳距离明显长于S组(P<0.05);创伤后7、14dA组大鼠潜伏期和游泳距离明显短于T组(P<0.05);T组BDNF、cAMP、CREB及pCREB浓度明显低于S组(P<0.05);A组BDNF、cAMP、CREB及pCREB浓度明显高于T组(P<0.05)。结论 SSA能够明显改善创伤性脑损伤大鼠认知功能,其机制可能与其激活cAMP/CREB信号通路及上调BDNF的表达有关。更多还原

【Abstract】 Objective To investigate the effects of Saikosaponin A(SSA)on cognitive function and cAMP/CREB signaling pathway and expression of BDNF in mice after traumatic brain injury.Methods Sixty SD male mice were randomized into three groups:shame operation group(group S,n=20),trauma group(group T,n=20)and SSA treatment group(group A,n=20).Mice received an administration of SSA 5mg/kg(group A)or equal volume saline(group S,group T)immediately and once daily for 5consecutive days after trauma.The cognitive function was detected by Morris water maze test on day 1,3,7and 14 after trauma.The hippocampal tissues were harvested after behavioral tests and homogenized for measuring the levels of brain derived neurophic factor(BDNF)and cyclic AMP(cAMP)by ELISA as well as the levels of cAMP-response element binding protein(CREB)and phosphorylation-cAMP-response element binding protein(pCREB)by western bolt.Results Compared with group S,the escape latency and swimming distance were significantly prolonged in group T on day 1,3,7and 14 and group A on day 1,3after trauma(P<0.05);while compared with group T,they were significantly shorter in group A on day 7,14 after trauma(P<0.05).Compared with group S,the levels of BDNF,cAMP,CREB and pCREB were significantly decreased in group T(P <0.05).Compared with group T,the levels of BDNF,cAMP,CREB and pCREB were significantly increased in group A(P<0.05).Conclusion SSA can significantly improve cognitive dysfunction in mice after traumatic brain injury,and the mechanism may be related to the activation of cAMP/CREB signaling pathway and up-regulation of BDNF.更多还原