木犀草素和芦丁组合物对帕金森病模型小鼠的防治作用  

Therapeutic Effect of the Mixture of Luteolin and Rutin in MPTP Induced Mouse Model of Parkinson's Disease

作　　者：何国荣[1] 成银霞[1] 穆鑫[1] 王月华[1] 孙岚[1] 方莲花[1] 杜冠华[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所“药物靶点研究与新药筛选”北京市重点实验室,北京100050

出　　处：《医药导报》2015年第5期578-584,共7页Herald of Medicine

基　　金：国家“重大新药创制”科技重大专项“十二五”课题(2013ZX09102106,2013ZX09508104,2012ZX09103-101-078);国家自然科学基金资助项目(81473383)

摘　　要：目的探讨木犀草素和芦丁组合物(MLR)对帕金森病(PD)模型小鼠的治疗作用及其机制。方法C57BL/6小鼠72只,随机分为6组(n=12),分别为正常对照组,模型对照组,美多巴组(50 mg·kg-1)和MLR小、中、大剂量组(140,280,560 mg·kg-1)。小鼠腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)30 mg·kg-1,建立亚急性PD模型。采用爬杆实验和悬挂实验评价小鼠肢体运动协调能力和体力;免疫组织化学法检测小鼠MPTP损伤通路中酪氨酸羟化酶(TH)阳性神经元数、多巴胺转运体(DAT)、胶质源性纤维蛋白(GFAP);高效液相色谱法检测中脑神经递质及其代谢产物含量。结果 MLR可显著改善PD模型小鼠运动协调能力(P<0.01或P<0.05)。MLR(280和560 mg·kg-1)可增加TH阳性神经元数目(可分别达到正常对照组的69.00%和77.95%,P<0.01)和DAT阳性神经元数目(可分别达到正常对照组的68.53%和70.40%,P<0.05),显著抑制星形胶质细胞反应性(P<0.01)。MLR各剂量组脑内单胺递质紊乱均显著改善。结论 MLR可显著改善MPTP致小鼠运动协调能力损伤,并可能通过调节脑内递质水平、抑制炎性反应、减轻神经元损伤发挥治疗PD的作用。Objective To study the therapeutic effect of the complex mixture of luteolin and rutin （ MLR） on 1-methyl-4-phenyL^-1,2,3,6-tetrahydropyridin （ MPTP） induced Parkinson’ s disease （ PD） mouse model. Methods Seventy-two C57BL/6 mice were divided into six groups randomly （ n=12 in each group）： the normal control , model control , madopar （50 mg·kg^-1） group, MLR at low （140 mg·kg^-1）, middle （280 mg·kg^-1） and high （560 mg·kg^-1） dose groups. PD mouse models were established by intraperitoneal injection of MPTP （ 30 mg · kg^-1 ） . Pole test and traction performance were recorded to access the body coordinate capability and strength. The tyrosine hydroxylase （TH）, dopamine transport protein （ DAT） , and glial fibrillary acidic protein （ GFAP ） positive cells were detected by immunohistochemical method. Dopamine （ DA ） , dihydroxyphenylacetic acid （ DOPAC ） , homovanilic acid （ HVA ） , 5-hydroxytryptamine （ 5-HT ） and 5-hydroxyindoleacetic acid （5-HIAA） in striatum were quantified by HPLC-ECD. Results MLR significantly ameliorated mouse motor coordination ability （P〈0. 01 or P〈0. 05）. MLR at 280 and 560 mg·kg^-1 could increase TH-positive neurons by 69. 00%and 77. 95% compared with the normal control group （P〈0. 01） and DAT-positive neurons by 68. 53% and 70. 40% compared with the normal control group（P〈0. 05）, and decrease GFAP-postive astrocyte reactivity. The treatment with MLR at three doses attenuated the monoamine neurotransmitter disorder. Conclusion MLR markedly improves MPTP caused movement coordinate ability injury in mice and exerts therapeutic action on PD by regulating neurotransmitters in brain, inhibiting the inflammatory reaction and alleviating the neuron injury.

关 键 词：木犀草素 芦丁 帕金森病 神经递质 

分 类 号：R286[医药卫生—中药学] R971[医药卫生—中医学]