镇肝熄风汤对帕金森病大鼠易激惹程度和结膜充血及NQO-1,TH的影响

目的:观察镇肝熄风汤对帕金森病肝大鼠易激惹程度和结膜充血的影响及可能机制。方法:将105只Wistar大鼠随机分为正常组,假手术组,模型组,司来吉兰组(0.9 mg·kg~(-1)·d~(-1)),镇肝熄风汤低、中、高剂量组(8,16,32 g·kg~(-1)·d~(-1)),每组15只。采用附子汤ig联合6-羟基多巴胺单侧损毁黑质法复制帕金森病肝阳上亢型病证结合大鼠模型,灌胃4周。蛋白质免疫印迹(Western blot)及实时荧光定量聚合酶链式反应(Real-time PCR)检测酪氨酸羟化酶(TH)和醌氧化还原酶-1(NQO-1)蛋白和mRNA表达。结果:与假手术组比较,帕金森病肝阳上亢证模型大鼠易激惹程度和结膜充血显著升高,中脑组织NQO-1蛋白和mRNA表达增加,而TH蛋白表达明显降低(P0.05)。与帕金森病肝阳上亢证模型组比较,镇肝熄风汤组大鼠易激惹程度和结膜充血显著降低,TH蛋白表达显著增加,NQO-1蛋白和mRNA表达均明显增加(P0.05),而司来吉兰组大鼠易激惹程度、结膜充血和中脑组织NQO-1蛋白表达无显著性差异。结论:镇肝熄风汤能显著改善帕金森病肝阳上亢证模型大鼠易激惹程度和结膜充血,其机制可能与上调大鼠中脑组织TH和NQO-1分子表达有关。

Effect of Zhengan Xifeng Tang in Parkinson's Disease Rats on Irritable Degree, Conjunctival Congestion and NQO-1, TH

Objective: To investigate the effects of Zhengan Xifeng Tang on the irritable degree and conjunctival congestion in Parkinson''s disease (PD) rats with syndrome of hyperactivity of liver-yang, and the possible mechanisms.Method: A total of 105 male Wistar rats were randomly divided into the normal control group, sham-operated group, model group, selegiline group (0.9 mg·kg^-1·d^-1), and high, medium and low-dose Zhengan Xifeng decoction groups (32, 16, 8 g·kg^-1), with 15 in each group. Rats were given 6-hydroxydopamine (6-OHDA) through intra-substantia nigra injection and Fuzitang through intragastric administration for four weeks to prepare rat model of PD with syndrome of hyperactivity of liver-yang. Caspase-3 activities were measured by using spectrophotometry. Real-time PCR and Western blot were used to analyze tyrosine hydroxylase (TH) and NADPH quinone oxidoreductase-1(NQO-1) mRNA and protein expressions.Result: Compared with sham-operated group, model group showed significant increases in irritable degree and conjunctival congestion, and NQO-1 mRNA and protein expressions in midbrain tissues, and decrease in TH protein expression (P<0.05). Compared with the model group, Zhengan Xifeng Tang group showed significant decreases in irritable degree and conjunctival congestion and increases in TH protein expression and NQO-1 mRNA and protein expressions (P<0.05). However, the above-mentioned markers were unaffected in selegiline group.Conclusion: Effect of liver-wind-tranquilizing of Zhengan Xifeng Tang may be correlated with up-regulation in gene expression of TH and NQO-1 in the midbrain of PD rats with syndrome of hyperactivity of liver-Yang.