镇肝熄风汤对帕金森病肝阳上亢证模型大鼠脑组织谷胱甘肽抗氧化系统的影响  

Effect of Zhen'gan Xifeng Decoction on Glutathion Antioxidant System in Midbrain of Parkinson's Disease Rats with Hyperactivity of Liver YANG Syndrome

作　　者：王晓丽[1] 朱兰芹[1] 綦艳秋[1] 孙影[1] 张红宇[1] 董妙先[1] WANG Xiaoli;ZHU Lanqin;QI Yanqiu;SUN Ying;ZHANG Hongyu;DONG Miaoxian(Qiqihar Medical University,Qiqihar Heilongjiang China161006)

机构地区：[1]齐齐哈尔医学院,黑龙江齐齐哈尔161006

出　　处：《中医学报》2018年第7期1289-1293,共5页Acta Chinese Medicine

基　　金：国家自然科学基金项目(81373629)

摘　　要：目的:观察镇肝熄风汤对帕金森病肝阳上亢证模型大鼠脑组织谷胱甘肽(glutathione,GSH)水平的影响,并分析其作用机制。方法:105只Wistar大鼠随机分为正常对照组,假手术组,模型对照组,镇肝熄风汤低剂量组、中剂量组、高剂量组,司来吉兰组,每组15只。采用附子汤灌胃加6-羟基多巴胺(6-hydroxydopamine,6-OHDA)单侧损毁黑质法双因素制备大鼠帕金森病肝阳上亢证模型。镇肝熄风汤干预4周后,采用紫外分光光度法检测GSH和氧化型谷胱甘肽(glutathione oxidized,GSSG)的含量,实时定量PCR法分析谷氨酸半胱氨酸连接酶修饰亚基(glutamate cysteine ligase modifier subunit,GCLm)和谷氨酸半胱氨酸连接酶催化亚基(glutamate cysteine ligase catalytic subunit,GCLc)mRNA表达,免疫印迹法分析GCLm和GCLc蛋白表达。结果:与模型对照组(0.26±0.23)比较,镇肝熄风汤低剂量组、中剂量组和高剂量组显著增加帕金森病肝阳上亢证模型大鼠中脑GSH/GSSG(1.62±0.24、2.02±0.23、3.54±0.40)。与模型对照组(Western blot:118.8±10.1,PCR:1.20±0.11)比较,镇肝熄风汤低剂量组、中剂量组和高剂量组显著上调了帕金森病肝阳上亢证模型大鼠中脑组织GCLc蛋白(140.8±8.3、150.4±7.6、158.6±9.1)和mRNA(1.80±0.19、1.98±0.13、2.08±0.17)表达,但并没有影响GCLm基因表达。结论:镇肝熄风汤可增加帕金森病肝阳上亢证大鼠脑组织GSH含量,在转录和翻译水平上调GCLc表达,这些作用可能是镇肝熄风汤抗帕金森病的机制之一。Objective：To investigate the effects of Zhen＇gan Xifeng decoction on glutathion content in the midbrain of Parkinson＇ s disease rats with Hyperactivity of Liver YANG Syndrome,and its possible mechanism. Methods：105 male Wistar rats were randomized into seven groups： the blank control,sham-operated group,model group,selegiline group,and Zhen＇ gan Xifeng Decoction group（32,16,or 8 g·kg-1 group. Rats were given 6-OHDA via intra-substantia nigra injection and Fuzi Decoction via intragastric administration to establish the rat model of Parkinson＇s disease with hyperactivity of Liver YANG Syndrome. Measurements of reduced glutathione（ GSH） and oxidized glutathione（ GSSG） content were performed using ultraviolet spectrophotometry. Real-time PCR and western blot were used to analyze the expression of GCLm and GCLc mRNA and protein. Results：Zhen＇gan Xifeng De-coction significantly increased GSH/GSSG Ratio,up-regulates the expression of GCLc mRNA and protein in the midbrain of Parkinson＇ s disease rats with syndrome of hyperactivity of liver-YANG. However,Zhen＇ gan Xifeng Decoction failed to influence the expression of GCLm mRNA and protein. Conclusions：GSH-mediated antioxidant actions of Zhen＇gan Xifeng Decoction may be attributable to the up-regulation of GCLc expression at levels of transcription and translation in the midbrain of Parkinson＇s disease rats with Hyperactivity of Liver YANG Syndrome,which may be one of the mechanisms of Zhen＇gan Xifeng Decoction fight against Parkinson＇s disease.

关 键 词：镇肝熄风汤 帕金森病 肝阳上亢证 谷胱甘肽 GCLc蛋白 GCLm蛋白 大鼠 

分 类 号：R285.5[医药卫生—中药学]