解郁1号方对卒中后大鼠脑内神经递质及海马组织Notch信号通路的影响

Effect of Jieyu No.1 Recipe on Neurotransmitter and Notch Signaling Pathway in Hippocampus of Rats After Stroke

目的分析解郁1号方对卒中后抑郁(PSD)大鼠行为学、脑内神经递质及海马组织Notch信号通路的影响。方法选取SPF级Wistar雄性大鼠60只,随机数字表法将大鼠分成4组,除正常组外,其他各组大鼠制备PSD模型,成功造模后阳性对照组大鼠灌胃2.33 mg·kg^-1的盐酸氟西汀药液,解郁1号方组灌胃2 g·kg^-1的解郁1号方药液,正常组和模型组大鼠灌胃等剂量蒸馏水,1次·d^-1,连续灌胃8周。观察各组大鼠行为学表征、脑组织内神经递质含量、Notch蛋白、Hes蛋白表达和Notch1、Hes1 mRNA表达,并检测各组大鼠海马组织内Notch信号路径功能情况。结果和正常组相比,给药后1、4、8周模型组大鼠神经功能评分升高;和模型组相比,给药后1、4、8周阳性对照组、解郁1号方组大鼠神经功能评分降低,差异有统计学意义(P<0.05);和正常组相比,模型组大鼠垂直运动、水平运动、清洁动作次数降低,粪便数、中央格停留时间升高;和模型组相比,阳性对照组、解郁1号方组大鼠垂直运动、水平运动、清洁动作次数升高,粪便数、中央格停留时间降低,差异有统计学意义(P<0.05);和正常组相比,模型组大鼠脑组织内5-羟吲哚乙酸(5-HIAA)、去甲肾上腺素(NE)、5-羟色氨酸(5-HT)及多巴胺(DA)含量降低;和模型组相比,阳性对照组、解郁1号方组大鼠脑组织内5-HIAA、NE、5-HT及DA含量升高,差异有统计学意义(P<0.05);和正常组相比,模型组大鼠开放时间、电流幅度、开放概率升高,关闭时间降低;和模型组相比,阳性对照组、解郁1号方组大鼠开放时间、电流幅度、开放概率升高,关闭时间降低,差异有统计学意义(P<0.05)。结论解郁1号方可提升PSD大鼠脑组织内神经递质含量,改善行为学表现,其作用机制可能和激活大鼠海马组织内Notch信号通路有关,从而加速神经功能的恢复。

OBJECTIVE To analyze the effects of Jieyu No.1(traditional Chinese medicine)on behavior,brain neurotransmitter and hippocampus Notch signaling pathway in post-stroke depression(PSD)rats.METHODS Sixty Wistar male rats of SPF grade were randomly divided into four groups.The PSD model was prepared by rats in other groups except the normal group.After successful modeling,the rats in the positive control group were intragastrically administered 2.33 mg·kg^-1 of fluoxetine hydrochloride solution,Jieyu No.1 prescription group 2 g·kg^-1 of Jieyu No.1 prescription liquid,rats in normal group and model group were given equal dose of distilled water,once/d,continuous irrigation Stomach for 8 weeks.The behavioral characterization,neurotransmitter content,Notch protein,Hes protein expression and Notch1 and Hes1 mRNA expression in the brain of each group were observed.The function of Notch signal pathway in hippocampus of each group was detected.RESULTS Compared with the normal group,the neurological function scores of the model group increased at 1,4,and 8 weeks after administration;compared with the model group,the positive control group and the Jieyu 1 group were administered 1,4,and 8 weeks after administration.The neurological function score of rats was decreased,and the difference was statistically significant(P<0.05).Compared with the normal group,the vertical movement,horizontal movement,and cleaning movements of the model group decreased,and the number of feces and the residence time of the central compartment increased.Compared with the model group,the positive control group and the Jieyu 1 group were larger.The vertical movement,horizontal movement,and cleaning movements of the rats increased,the number of stools and the residence time of the central compartment decreased,and the difference was statistically significant(P<0.05).Compared with the normal group,the 5-HIAA in the brain tissue of the model group was the contents of NE,5-HT and DA were decreased.Compared with the model group,the contents of 5-HIAA,NE,5-HT and DA in the brain of rats in the positive control group and Jieyu No.1 group were increased.The difference was statistically significant(P<0.05);compared with the normal group,the model group rats increased open time,current amplitude,open probability,and closed time decreased;compared with the model group,positive control group,Jieyu 1 square group rats open time,flow amplitude,open probability increased,reducing the off-time,the difference was statistically significant(P<0.05).CONCLUSION Jieyu No.1 can increase the neurotransmitter content in the brain tissue of PSD rats and improve the behavioral behavior.The mechanism may be related to the activation of Notch signaling pathway in rat hippocampus,thus accelerating the recovery of nerve function.