逍遥散对慢性应激下AD复合模型大鼠海马组织的作用及其机制

The Effect and its Mechanism of Xiaoyao San on Hippocampal Tissuein AD Complex Model Rats under Chronic Stress

目的:探讨逍遥散对慢性应激下AD复合模型大鼠海马组织的作用及其机制。方法:将SD大鼠随机分为正常对照组、假手术组、模型组及逍遥散高、中、低剂量组。除正常对照组与假手术组外,其余各组采用海马区注射NaN3加慢性应激刺激复制慢性应激下AD复合模型,观察各组大鼠行为学和海马组织内相关蛋白表达情况。结果:与正常对照组比较,模型组的糖水偏好率和认知能力均显著降低(P<0.05或P<0.01);与模型组比较,逍遥散各剂量均可显著改善复合模型的糖水偏好率与认知障碍(P<0.01)。与正常对照组比较,模型组GR、BDNF、FKBP52蛋白表达降低,FKBP51蛋白表达和Aβ的沉积显著升高(P<0.05或P<0.01);与模型组比较,高、中剂量逍遥散可显著升高GR、BDNF、FKBP52蛋白表达,减少FKBP51蛋白表达和Aβ的沉积。结论:高、中剂量逍遥散均可显著改善慢性应激下AD复合模型大鼠的糖水偏好率与认知障碍,减少海马组织中Aβ蛋白的沉积,该作用可能是通过上调海马组织内GR、BDNF、FKBP52蛋白表达,下调FKBP51蛋白表达实现的。

Objective:To investigate the effect and mechanism of Xiaoyao san on hippocampal tissue of AD complex model rats under chronic stress.Methods:SD rats were randomly divided into normal control group,sham operation group,model group,high-and medium-,low-dose groups of Xiaoyao san.In addition to the normal control group and the sham operation group,the other groups were injected with NaN3 in the hippocampus and stimulated by chronic stress to replicate the AD complex model under chronic stress.The behavior of rats in each group and the expressions of related proteins in the hippocampus were observed.Results:Compared with the normal control group,the sugar water preference rate and cognitive ability of the model group were significantly decreased(P<0.05 or P<0.01).Compared with model group,Xiaoyao san with different doses could significantly improve the sugar water preference rate and cognitive impairment of model rats(P<0.05 or P<0.01).Compared with the normal control group,the protein expressions of GR,BDNF and FKBP52 in the model group were decreased,while the expression of FKBP51 protein and the deposits of Aβwere significantly increased(P<0.05 or P<0.01).Compared with the model group,high-and medium-dose groups of Xiaoyao san significantly increased the expressions of GR,BDNF and FKBP52 proteins,decreased the expression of FKBP51 protein and the deposits of Aβ.Conclusion:The high-and medium-doses of Xiaoyao san can significantly improve the sugar water preference rate and cognitive impairment in the AD complex model rats under chronic stress,decrease the deposits of Aβ,the effect may be realized by up-regulating the protein expressions of GR,BDNF and FKBP52 and down-regulating the protein expression of FKBP51 in the hippocampus.