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[摘要]
目的:本研究主要观察镇肝熄风汤对帕金森病肝阳上亢证大鼠中脑Akt 及其下游靶分子GSK-3β磷酸化的影响。方法:105只大鼠随机分为对照组、假手术组、模型组、镇肝熄风汤高、中、低剂量组和司来吉兰组。采用6-OHDA中脑微量注射合并附子汤灌胃制备帕金森病肝阳上亢证模型,采用分光光度法检测中脑组织caspase-3活性,Western blot检测脑组织Akt和GSK-3β磷酸化水平。结果:与假手术组比较,帕金森病肝阳上亢证大鼠中脑caspase-3活性明显增强,Akt和GSK-3β磷酸化水平明显升高,而镇肝熄风汤组中脑caspase-3活性明显减弱,Akt和GSK-3β磷酸化水平明显升高。结论:镇肝熄风汤能够减弱帕金森病肝阳上亢证大鼠中脑caspase-3活性,其机制可能与Akt 活化和GSK-3β失活有关。
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[Abstract]
The aim of this study was to investigate the effects of Zhengan Xifeng decoction(ZGXFD)on the phosphorylation of Akt and its downstream target molecule GSK-3β in the midbrain of Parkinson’s disease(PD)rats with the syndrome of liver-yang hyperactivity.A total of 105 pathogen-free male Wistar rats were randomly divided into seven groups:the control group,the sham-operated group,the model group,the ZGXFD high-,medium- and low-dose groups and the selegiline group.Microinjection of 6-OHDA into substantia nigra and the intragastric administration of Fuzi decoction were given to establish the rat model of Parkinson’s disease with syndrome of liver-yang hyperactivity.The activity of caspase-3 was detected using spectrophotometry.The phosphorylation of Akt and GSK-3β in the midbrain was analyzed by western blot.It was found that the activity of caspase-3 in the midbrain was enhanced while the phosphorylation of Akt and GSK-3β was increased in the PD rats of the model group compared with the sham-operated group.The activity of caspase-3 in the midbrain was inhibited and the phosphorylation of Akt and GSK-3β was up-regulated in the ZGXFD groups.In conclusion,it was demonstrated that the anti-apoptotic effects of ZGXFD may activate the Akt and suppress of the activity of GSK-3β in the midbrain of PD r ats with the syndrome of liver-yang hyperactivity.
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