镇肝熄风汤对帕金森病肝阳上亢证大鼠中脑Akt和GSK-3β磷酸化的影响

Effects of Zhengan Xifeng Decoction on the Phosphorylation of Akt and GSK-3β in the Midbrain in Rats with Parkinson's Disease and the Syndrome of Liver-Yang Hyperactivity

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。

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. Microinjeetion 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 rats with the syndrome of liver-yang hyperactivity.