越鞠丸对创伤后大鼠焦虑行为和海马BDNF及5-HT受体表达的影响

Yueju pill had an effect on anxious behavior and hippocampal BDNF and 5-HT receptor in posttraumatic rats

目的探讨越鞠丸灌胃对创伤后应激障碍(PTSD)大鼠的焦虑行为和海马区BDNF及五羟色胺(5-HT)表达的影响。方法通过掠食性气味诱导PTSD大鼠,将40只雄性Wistar大鼠随机分为5组:正常组、PTSD组和在PTSD基础上进行治疗的3组,即为地西泮治疗组1(阳性对照,0.25 ml静脉注射)、越鞠丸治疗组2(30μg·kg-1·10 ml-1灌胃)、越鞠丸治疗组3(90μg·kg-1·10 ml-1,灌胃);旷场实验测定大鼠的自主活动能力和焦虑行为,高架十字迷宫测定大鼠的焦虑行为和水迷宫实验测定大鼠恐惧记忆障碍。实时定量PCR和蛋白免疫印迹检测大鼠海马组织的BDNF、5-HT 1A和5-HT2A的表达。结果与正常组比较,PTSD组的焦虑行为明显加强,差异均有统计学意义(均P<0.05);30和90μg·kg-1·10 ml-1的越鞠丸灌胃治疗明显抑制PTSD大鼠的僵立时间、闭合臂停留时间、闭合臂停留时间比、逃避潜伏期;30和90μg·kg-1·10 ml-1的越鞠丸灌胃治疗增加大鼠的总跨格数、中央格停留时间、开放臂停留时间、开放臂停留时间比例(均P<0.05);而且,PTSD组低表达的BDNF、5-HT1A、5-HT2A的mRNA和蛋白水平均被30和90μg·kg-1·10 ml-1的越鞠丸上调(均P<0.05)。结论越鞠丸可明显降低PTSD大鼠的恐惧记忆和自主活动、改善焦虑行为,并维持PTSD大鼠海马组织中的BDNF、5-HT1A、5-HT2A的表达。

Objective To investigate the effect of Yueju pill gavage on anxiety behavior and expression of BDNF and 5-HT in hippocampus in rats with post-traumatic stress disorder(PTSD).Methods PTSD rats were induced by predatory odor,and 40 male Wistar rats were randomly divided into 5 groups:normal group,PTSD group,and treatment based on PTSD:Diazepam treatment group 1(positive control,0.25 ml intravenous injection),Yueju pill treatment group 2(30μg·kg-1·10 ml-1,gavage),Yueju pill treatment group 3(90μg·kg-1·10 ml-1,gavage).Open field experiments were performed to determine the autonomic activity and anxiety of rats.An elevated cross maze was used to determine anxiety in rats and a water maze test was used to determine fear and memory impairment in rats.The expressions of brain-derived neurotrophic factor(BDNF),serotonin(5-HT)receptor 1 A and 5-HT2 A in hippocampus of rats were detected by real-time quantitative PCR and western blot.Results Compared with the normal group,the anxiety behavior of the PTSD group was significantly enhanced,and the differences were statistically significant(all P<0.05);30 and 90μg·kg-1·10 ml-1 of Yueju Pill intragastrically significantly inhibited the stagnation time,closed-arm dwell time,closed-arm dwell time ratio,and escape latency of PTSD rats;30 and 90μg·kg-1·10 ml-1 of Yueju pill intragastrically increased the total span number,central cell retention time,open arm retention time,and open arm retention time ratio(all P<0.05).Moreover,the mRNA and protein levels of BDNF,5-HT1 A,and 5-HT2 A that were under-expressed in the PTSD group were up-regulated by 30 and90μg·kg-1·10 ml-1 of Yueju pills(all P<0.05).Conclusion Yueju Pill can significantly reduce fear memory and autonomic activity,improve anxiety behavior,and maintain the expression of BDNF,5-HT1 A,5-HT2 A in hippocampus of PTSD rats.