目的：观察镇肝熄风汤对帕金森病（Parkinson’s Disease，PD）肝阳上亢证模型大鼠旋转行为的影响，探讨其可能的作用机制。方法：采用附子汤灌胃联合6-OHDA偏侧毁损制备PD肝阳上亢证大鼠模型，肝熄风汤灌胃给药28天。观察阿朴吗啡诱导的大鼠旋转行为，采用实时荧光定量PCR检测编码核因子E2相关因子2（Transcription Factor NF-E2-Related Factor 2，Nrf2）基因Nfe2l2和编码血红素加氧酶-1（Heme Oxygenase 1，HO-1）的基因Hmox-1的表达，采用Western blot检测Keap1蛋白表达。结果：与模型组比较，镇肝熄风汤显著减少了阿朴吗啡诱导的PD 大鼠旋转行为，上调了模型大鼠中脑黑质Nfe2l2和Hmox-1 mRNA表达，抑制了Keap1蛋白表达。与假手术组比较，模型组大鼠中脑黑质Nfe2l2和Hmox-1 mRNA的代偿性增加也达到了统计学意义，但Keap1蛋白表达无显著性改变。结论：镇肝熄风汤可改善PD肝阳上亢证大鼠的行为学改变，增加中脑黑质Nfe2l2和Hmox-1 mRNA表达，抑制了Keap1蛋白表达，提示镇肝熄风汤抗PD 的作用可能与其抗氧化作用有关。

The aim of this study was to explore the effects of ZGXF decoction on amphetamine-induced rotation in PD rats with syndrome of liver-yang hyperactivity,and its mechanism involved. Rats received 6-OHDA administration via intra-substantia nigra injection and were intragastrically treated by Fu Zi decoction to establish the PD model with the syndrome of liver-yang hyperactivity.Three doses of ZGXF decoction or selegiline were given by a 28-day intragastric administration. The rats were tested for amphetamine-induced rotation asymmetry.In addition,real-time PCR were adopted to analyze the expressions of Nfe2l2 and Hmox-1 mRNAs,while western blot to analyze the expression of Keap1 protein.As a result,it was found that ZGXF decoction dose-dependently attenuated amphetamine-induced rotation,up-regulated the expressions of Nfe2l2 and Hmox-1 mRNAs,and down-regulated the expression of Keap1 protein in the substantia nigra in PD rats with syndrome of liver-yang hyperactivity.It was suggested that anti-PD effects of ZGXF decoction be attributed to the up-regulation of Nfe2l2 and Hmox-1 mRNAs and the down-regulation of Keap1 protein,being associated with oxidative stress,in the substantia nigra of PD rats with syndrome of liver- yang hyperactivity.

国家自然科学基金委面上项目（81373629）：基于PI3K/Akt/GSK-3β信号通路的镇肝熄风法抑制帕金森病氧化应激损伤的机制研究，负责人：董妙先。