中药复方地黄方对帕金森病异动症模型大鼠△FosB mRNA及蛋白表达的影响
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摘要
目的:探讨中药复方地黄方对帕金森病(PD)异动症(LID)模型大鼠纹状体内△FosB mRNA及蛋白表达的影响,寄以探索PD的发病机制,为临床PD的防治提供依据。方法:采用6-羟基多巴胺(6-OHDA)偏侧损毁黑质制备PD大鼠模型,在成功制备PD大鼠模型基础上,腹腔注射左旋多巴+苄丝阱制备LID大鼠模型。将大鼠随机分为LID模型组、复方地黄方组,并纳入正常对照组、假手术组、PD模型组,在治疗4周后取纹状体,应用Real-time PCR和Western blot测定各组大鼠纹状体内△FosB mRNA及蛋白表达情况。结果:PD模型和LID模型大鼠纹状体中△FosB mRNA及蛋白相对表达水平较正常对照组、假手术组均显著升高(P<0.01),且LID模型大鼠显著高于PD模型大鼠(P<0.01);复方地黄方干预后,其大鼠纹状体中△FosB mRNA及蛋白相对表达水平显著降低(P<0.01)。结论:复方地黄方可能通过调节基底神经环路,减低纹状体区强啡肽原的表达,从而降低△FosB mRNA和蛋白的表达,减轻神经毒性,缓解PD及LID。
Objective: To investigate the effects of Compound Dihuang Decoction on expression of △Fos B mRNA and protein in the striatum of rats with Parkinson's disease(PD) and levodopa-induced dyskinesia(LID), so as to explore the pathogenesis of PD and provide evidence for the prevention and treatment of PD. Methods: The rats model of PD were established by the method of laterallydamagingsubstantia nigra with 6-hydroxydopamine(6-OHDA), and the rats model of LID were prepared by intraperitoneal injection of levodopa and benserazide on PD rats. Rats were randomly divided into control group, shamsurgery group, PD group, LID group and Compound Dihuang Decoction group. After treating the rats for 4 weeks, the expression of △Fos B mRNA and protein were detected with Real-time PCR and Western blot. Results: The expressions of △Fos B mRNA and protein were significantly higher than control and sham group(P<0.01), and LID model rats was significantly higher than PD rats(P<0.01). After treatment with Compound Dihuang Decoction, the expressions of △Fos B mRNA and protein were obviously decreased(P<0.01). Conclusion: Compound Dihuang Decoction may alleviate neurotoxicity, Parkinson's disease and levodopa-induced dyskinesia by modulating the basilar nerve loop, reducing the expression of PDyn in striatum region to decrease △Fos B protein and mRNA expression.
Objective: To investigate the effects of Compound Dihuang Decoction on expression of △Fos B mRNA and protein in the striatum of rats with Parkinson's disease(PD) and levodopa-induced dyskinesia(LID), so as to explore the pathogenesis of PD and provide evidence for the prevention and treatment of PD. Methods: The rats model of PD were established by the method of laterallydamagingsubstantia nigra with 6-hydroxydopamine(6-OHDA), and the rats model of LID were prepared by intraperitoneal injection of levodopa and benserazide on PD rats. Rats were randomly divided into control group, shamsurgery group, PD group, LID group and Compound Dihuang Decoction group. After treating the rats for 4 weeks, the expression of △Fos B mRNA and protein were detected with Real-time PCR and Western blot. Results: The expressions of △Fos B mRNA and protein were significantly higher than control and sham group(P<0.01), and LID model rats was significantly higher than PD rats(P<0.01). After treatment with Compound Dihuang Decoction, the expressions of △Fos B mRNA and protein were obviously decreased(P<0.01). Conclusion: Compound Dihuang Decoction may alleviate neurotoxicity, Parkinson's disease and levodopa-induced dyskinesia by modulating the basilar nerve loop, reducing the expression of PDyn in striatum region to decrease △Fos B protein and mRNA expression.
引文
[1]滕龙,洪芳,何建成.阴虚动风证帕金森病异动症大鼠大麻素CBl受体变化及复方地黄方的干预作用.中国实验动物学报,2016,24(1):31-36
[2]Cavanaugh J T,Ellis T D,Earhart G M,et al.To ward Under standing Ambulatory Activity Decline in Parkinson’s disease.Phys Ther,2015,95(8):1142-1150
[3]陈生弟.帕金森病运动并发症的防治策略.中华老年医学杂志,2016,35(4):343-346
[4]张莉,罗振中,刘晶,等.帕金森病异动症研究进展.中华医学杂志,2016,96(41):3350-3352
[5]刘洋,焦玥,孙丹丹,等.首乌方对左旋多巴诱发异动症模型大鼠脑内氨基酸类神经递质水平的影响.中国比较医学杂志,2016,26(1):7-13
[5]陈贵勤.MEK抑制剂的抗异动症效应与△Fos B等信号分子表达改变相关.成都:中华医学会第十八次全国神经病学学术会议,2015
[6]Ah-Reum Doo,Seung-Nam Kim,Dae-Hyun Hahm,et al.Gastrodia elata Blume alleviates L-DOPA-induced dyskinesia by normalizing FosB and ERK activation in a 6-OHDA-lesioned Parkinson’s disease mouse model.BMC Complementary and Alternative Medicine,2014,14(1):107
[7]滕龙,洪芳,何建成.阴虚动风证帕金森病异动症大鼠大麻素CBl受体变化及复方地黄方的干预作用.中国实验动物学报,2016,24(1):31-36
[8]Long Teng,Fang Hong,Jiancheng He.Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson’s disease.Neural Regeneration Research,2014,9(4):407-412
[9]孙瑞元.定量药理学.北京:人民卫生出版社,1991:49-58
[10]Ungerstedt U.6-Hydroxy-dopamine induced degeneration of central monoamine neurons.Eur J Pharmacol,1968,5(1):107-110
[11]包新民,舒斯云.大鼠脑立体定位图谱.北京:人民卫生出版社,1991:49-58
[12]滕龙,洪芳,何建成.中药复方地黄方对帕金森病异动症模型大鼠神经行为学动态变化的研究.浙江中医杂志,2016,51(6):411-413
[13]Nicola S,Micaela M,Anna R.The 6-Hydroxydopamine model of Parkinson’s disease.Neurotoxicity Research,2007,11(3):151-167
[14]王弘,乔德才,刘晓莉.A2AR/D2DR在运动调节帕金森病基底神经节功能紊乱中的作用研究进展.中国老年学杂志,2017,37(1):222-225
[15]朱燚,武衡.谷氨酸和γ-氨基丁酸在帕金森病中的作用机制研究进展.现代医药卫生,2015,31(21):3259-3261
[16]刘佳,段春礼,杨慧.帕金森病发病机制与治疗研究进展.生理科学进展,2015,46(3):163-169
[17]洪芳.阴虚动风证帕金森病异动症大鼠多巴胺D1、D2受体变化的研究.上海:上海中医药大学,2013
[18]Sgroi S,Capper-Loup C,Paganetti P,et al.Enkephalin and dynorphin neuropeptides are differently correlated with locomotor hypersensitivity and levodopa-induced dyskinesia in parkinsonian rats.Exp Neurol,2016,280(10):80-88
[19]Doo A R,Kim S N,Hahm D H,et al.Gastrodia elata Blume alleviates L-DOPA-induced dyskinesia by normalizing FosB and ERK activation in a 6-OHDA lesioned Parkinson’s disease mouse model.BMC Complement Altern Med,2014,20(14):1-8
[20]梁建庆,何建成.病证结合大鼠帕金森病模型构建初探.中华中医药杂志,2016,31(5):1854-1857
[21]刘金涛,陈叶,何建成,等.绿茶对1-甲基-4-苯基-1,2,3,6-四氢吡啶致帕金森病小鼠模型神经行为学的防治作用.国老年学杂志,2016,36(13):3119-3121
[2]Cavanaugh J T,Ellis T D,Earhart G M,et al.To ward Under standing Ambulatory Activity Decline in Parkinson’s disease.Phys Ther,2015,95(8):1142-1150
[3]陈生弟.帕金森病运动并发症的防治策略.中华老年医学杂志,2016,35(4):343-346
[4]张莉,罗振中,刘晶,等.帕金森病异动症研究进展.中华医学杂志,2016,96(41):3350-3352
[5]刘洋,焦玥,孙丹丹,等.首乌方对左旋多巴诱发异动症模型大鼠脑内氨基酸类神经递质水平的影响.中国比较医学杂志,2016,26(1):7-13
[5]陈贵勤.MEK抑制剂的抗异动症效应与△Fos B等信号分子表达改变相关.成都:中华医学会第十八次全国神经病学学术会议,2015
[6]Ah-Reum Doo,Seung-Nam Kim,Dae-Hyun Hahm,et al.Gastrodia elata Blume alleviates L-DOPA-induced dyskinesia by normalizing FosB and ERK activation in a 6-OHDA-lesioned Parkinson’s disease mouse model.BMC Complementary and Alternative Medicine,2014,14(1):107
[7]滕龙,洪芳,何建成.阴虚动风证帕金森病异动症大鼠大麻素CBl受体变化及复方地黄方的干预作用.中国实验动物学报,2016,24(1):31-36
[8]Long Teng,Fang Hong,Jiancheng He.Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson’s disease.Neural Regeneration Research,2014,9(4):407-412
[9]孙瑞元.定量药理学.北京:人民卫生出版社,1991:49-58
[10]Ungerstedt U.6-Hydroxy-dopamine induced degeneration of central monoamine neurons.Eur J Pharmacol,1968,5(1):107-110
[11]包新民,舒斯云.大鼠脑立体定位图谱.北京:人民卫生出版社,1991:49-58
[12]滕龙,洪芳,何建成.中药复方地黄方对帕金森病异动症模型大鼠神经行为学动态变化的研究.浙江中医杂志,2016,51(6):411-413
[13]Nicola S,Micaela M,Anna R.The 6-Hydroxydopamine model of Parkinson’s disease.Neurotoxicity Research,2007,11(3):151-167
[14]王弘,乔德才,刘晓莉.A2AR/D2DR在运动调节帕金森病基底神经节功能紊乱中的作用研究进展.中国老年学杂志,2017,37(1):222-225
[15]朱燚,武衡.谷氨酸和γ-氨基丁酸在帕金森病中的作用机制研究进展.现代医药卫生,2015,31(21):3259-3261
[16]刘佳,段春礼,杨慧.帕金森病发病机制与治疗研究进展.生理科学进展,2015,46(3):163-169
[17]洪芳.阴虚动风证帕金森病异动症大鼠多巴胺D1、D2受体变化的研究.上海:上海中医药大学,2013
[18]Sgroi S,Capper-Loup C,Paganetti P,et al.Enkephalin and dynorphin neuropeptides are differently correlated with locomotor hypersensitivity and levodopa-induced dyskinesia in parkinsonian rats.Exp Neurol,2016,280(10):80-88
[19]Doo A R,Kim S N,Hahm D H,et al.Gastrodia elata Blume alleviates L-DOPA-induced dyskinesia by normalizing FosB and ERK activation in a 6-OHDA lesioned Parkinson’s disease mouse model.BMC Complement Altern Med,2014,20(14):1-8
[20]梁建庆,何建成.病证结合大鼠帕金森病模型构建初探.中华中医药杂志,2016,31(5):1854-1857
[21]刘金涛,陈叶,何建成,等.绿茶对1-甲基-4-苯基-1,2,3,6-四氢吡啶致帕金森病小鼠模型神经行为学的防治作用.国老年学杂志,2016,36(13):3119-3121