β-细辛醚减少美多芭在PD模型大鼠中的使用剂量

β-Asarone Reduces Use Dosage of Madopar in Parkinson's Disease Model Rats

【目的】观察石菖蒲挥发油主要有效成分β-细辛醚联合小剂量美多芭对6-羟基多巴胺(6-OHDA)诱导帕金森病(PD)模型大鼠的疗效是否与常规剂量美多芭疗效相当及联合用药对单胺类神经递质和多巴胺(DA)合成酶的影响。【方法】将70只大鼠随机分为7组,即假手术组、模型组、美多芭组(剂量为75 mg/kg)、β-细辛醚组(剂量为15 mg/kg)、β-细辛醚+美多芭组(15 mg/kg+75 mg/kg)、β-细辛醚+1/2美多芭组(15 mg/kg+37.5 mg/kg)、β-细辛醚+1/4美多芭组(15 mg/kg+18.75 mg/kg),每组10只。除假手术组外,其他组别大鼠均给予立体注射6-OHDA复制PD模型。成功造模后,每天分2次灌胃给药,给药30 d。测定大鼠行为学改变,高效液相色谱(HPLC)法测定纹状体、血清内单胺类神经递质,酶联免疫吸附分析(ELISA)检测血清、中脑内多巴脱羧酶(DDC)含量及肝肾功能,流式细胞术测定中脑内酪氨酸羟化酶(TH)的表达率,苏木素—伊红(HE)染色观察肝肾组织。【结果】β-细辛醚+1/2美多芭组与美多芭组在旷场实验、转棒实验、步态实验等行为学方面无明显差异(P>0.05),联合用药可提高DA等神经递质及TH相关酶含量,降低血清内DDC的含量,同时可减轻肝肾功能损害。【结论】β-细辛醚能够减少美多芭在6-OHDA诱导的PD模型大鼠中的治疗使用剂量,可能是通过提高脑组织内TH含量,抑制血清内DDC的含量来增加脑组织内单胺类神经递质的含量。

Objective To explore whether the effect of β-asarone(the main component of volatile oils from Rhizoma Acori Tatarinowii)combined with low-dose madopar on 6-hydroxydopamine(6-OHDA)-induced Parkinson’s disease(PD)rats equally matched the therapeutic effect of routine dosage of madopar,and to observe its effect on neurotransmitter and dopamine(DA)synthase. Methods Seventy rats were randomly divided into 7 groups:sham operation group,model group,madopar group(at the dosage of 75 mg/kg),β-asarone group(at the dosage of 15 mg/kg),β-asarone + madopar group(15 mg/kg + 75 mg/kg),β-asarone + 1/2 madopar group(15 mg/kg +37.5 mg/kg),and β-asarone + 1/4 madopar group(15 mg/kg + 18.75 mg/kg),10 rats in each group. Except for sham operation group,PD models were established by stereotactic injection of 6-OHDA in the other groups. After successful modeling, intragastric administration of corresponding drug twice a day was carried out in various groups,the treatment covering 30 d. Behavior of the rats was measured,monoamine neurotransmitters in striatum and serum were determined by high performance liquid chromatography(HPLC),dopa decarboxylase(DDC)in serum and midbrain,and hepatic-renal function were detected by enzyme-linked immunosorbent assay(ELISA),tyrosine hydroxylase(TH)expression rate in midbrain was detected by flow cytometry,and liver and kidney tissues were observed by hematoxylin-eosin(HE)staining. Results There was no significant difference in behaviors involving open field test,rotarod test,gait test between β-asarone +1/2 madopar group and madopar group(P>0.05). The combination of β-asarone + 1/2 madopar increased the contents of DA and TH,decreased the content of DDC in serum,and relieved the damage of liver and kidney function. Conclusion β-asarone can reduce the dosage of madopar in treating 6-OHDA-induced PD model rats, its mechanism being possibly related with increasing TH content in brain tissues and inhibiting DDC content in serum thus to increase the neurotransmitter content in brain tissues.