芍药甘草汤对帕金森病大鼠脑内神经递质及肌强直的影响
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摘要
目的:探讨芍药甘草汤对帕金森病大鼠脑内神经递质及肌强直的影响。方法:将76只健康雄性SD大鼠随机分为正常对照组12只,6-OHDA造模组64只(按照既往实验结果成模率约67%)。采用单侧纹状体损毁术建立帕金森病(Parkinson′s disease,PD)大鼠模型,随机分为模型组、美多芭组、芍药甘草汤组,每组各12只,分别予以美多巴(20 mg·kg~(-1))、芍药甘草汤(芍药62.5 g+甘草62.5 g)灌胃4周。治疗后4周进行大鼠自主活动度检测,采用肌电图记录PD大鼠腓总神经电生理改变,观察大鼠脑内神经递质多巴胺(dopamine,DA)、高香草酸(homovaniilic acid,HVA)、乙酰胆碱(acetylcholine,Ach)含量的变化,并检测黑质酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性细胞的表达情况。结果:美多芭组与芍药甘草汤组自由活动度比较无显著差异(P>0.05),但两组自主活动度均显著高于模型组,且均低于正常对照组,差异均具有统计学意义(P<0.05);治疗前,模型组、美多芭组、芍药甘草汤组近端、远端肌肉动作电位传导速度(motor conduction velocity,MCV)均显著低于正常对照组(P<0.05),治疗后,美多芭组、芍药甘草汤组近端、远端肌肉动作电位MCV逐渐增高,至治疗第4周,美多芭组、芍药甘草汤、正常对照组的近端MCV比较无显著差异(P>0.05),但3组均显著高于模型组(P<0.05);芍药甘草汤组远端MCV高于美多芭组,美多芭组高于模型组(P<0.05),但芍药甘草汤组与正常对照组比较无显著差异(P>0.05);正常对照组脑黑质内神经元排列整齐,核仁清楚,模型组神经元部分肿胀,且核仁不明显,神经纤维排列紊乱,结构疏松;美多芭组相对模型组,其神经元肿胀减轻,排列较为整齐,芍药甘草汤组神经元则明显减轻,排列整齐。结论:芍药甘草汤可有效改善帕金森病大鼠脑内神经递质水平,并缓解肌强直,提高PD大鼠自主活动度。
Objective:To investigate the effects of Shaoyao Gancao Decoction on neurotransmitters and myotonia in rats with Parkinson′s disease.Methods:Seventy-six healthy male Sprague-Dawley rats were randomly divided into normal control group(n=12) and OHDA model group(n=64).According to the previous experimental results,the mold rate is about 67%.The unilateral striatum was used to establish the stenosis.Parkinson′s disease(PD) rat model was randomly divided into model group,Medoca group and Shaoyao Gancao Decoction group,with 12 rats in each group,which were treated with Madopar(20 mg·kg~(-1)) and Shaoyao Gancao Decoction(Shaoyao 62.5 g+Gancao 62.5 g) and all the groups were administered for 4 weeks.The autonomic activity of the rats was detected 4 weeks.After treatment,the electrophysiological changes of the common peroneal nerve of PD rats were recorded with electromyography.The neurotransmitters dopamine(DA),homovanilic acid(HVA),changes in the content of acetylcholine(Ach) and the expression of tyrosine hydroxylase(TH) positive cells in the rat brain were detected and observed.Results:There was no significant difference in the free activity between the Meiduoba group and the Shaoyao Gancao Decoction group(P>0.05),but the autonomic activity of the two groups was significantly higher than that of the model group(P<0.05).Before treatment,the motor conduction velocity(MCV) of the proximal and distal muscles of the model group,Meiduoba group and Shaoyao Gancao decoction group were significantly lower than that of the normal control group(P<0.05).After treatment,the MCV of the proximal and distal muscles of the patients in the Meiduoba group and the Shaoyao Gancao Decoction group gradually increased.By the fourth week of treatment,the proximal MCV of the Midotaba group,the Shaoyao Gancao Decoction and the normal control group were compared.There was no significant difference(P>0.05),but the three treatment groups were significantly higher than that of the model group(P<0.05).The distal MCV of the Shaoyao Gancao Decoction group was higher than that of the Meiduoba group,and the Meiduoba group was higher than the model group(P<0.05).However,there was no significant difference between the Shaoyao Gancao Decoction group and the normal control group(P>0.05).The neurons in the substantia nigra of the normal control group were arranged neatly,the nucleolus was clear,the neurons in the model group were partially swollen,and the nucleolus was not obvious.The nerve fibers are disorderly arranged and the structure is loose.Compared with the model group,the swelling of neurons was relieved and was arranged more neatly of Meiduoba group,and that of the Shaoyao Gancao Decoction group was more significantly improved.Conclusion:Shaoyao Gancao Decoction can effectively improve the neurotransmitter levels in the brain of rats with Parkinson′s disease,relieve muscle rigidity and improve the autonomic activity of PD rats.
Objective:To investigate the effects of Shaoyao Gancao Decoction on neurotransmitters and myotonia in rats with Parkinson′s disease.Methods:Seventy-six healthy male Sprague-Dawley rats were randomly divided into normal control group(n=12) and OHDA model group(n=64).According to the previous experimental results,the mold rate is about 67%.The unilateral striatum was used to establish the stenosis.Parkinson′s disease(PD) rat model was randomly divided into model group,Medoca group and Shaoyao Gancao Decoction group,with 12 rats in each group,which were treated with Madopar(20 mg·kg~(-1)) and Shaoyao Gancao Decoction(Shaoyao 62.5 g+Gancao 62.5 g) and all the groups were administered for 4 weeks.The autonomic activity of the rats was detected 4 weeks.After treatment,the electrophysiological changes of the common peroneal nerve of PD rats were recorded with electromyography.The neurotransmitters dopamine(DA),homovanilic acid(HVA),changes in the content of acetylcholine(Ach) and the expression of tyrosine hydroxylase(TH) positive cells in the rat brain were detected and observed.Results:There was no significant difference in the free activity between the Meiduoba group and the Shaoyao Gancao Decoction group(P>0.05),but the autonomic activity of the two groups was significantly higher than that of the model group(P<0.05).Before treatment,the motor conduction velocity(MCV) of the proximal and distal muscles of the model group,Meiduoba group and Shaoyao Gancao decoction group were significantly lower than that of the normal control group(P<0.05).After treatment,the MCV of the proximal and distal muscles of the patients in the Meiduoba group and the Shaoyao Gancao Decoction group gradually increased.By the fourth week of treatment,the proximal MCV of the Midotaba group,the Shaoyao Gancao Decoction and the normal control group were compared.There was no significant difference(P>0.05),but the three treatment groups were significantly higher than that of the model group(P<0.05).The distal MCV of the Shaoyao Gancao Decoction group was higher than that of the Meiduoba group,and the Meiduoba group was higher than the model group(P<0.05).However,there was no significant difference between the Shaoyao Gancao Decoction group and the normal control group(P>0.05).The neurons in the substantia nigra of the normal control group were arranged neatly,the nucleolus was clear,the neurons in the model group were partially swollen,and the nucleolus was not obvious.The nerve fibers are disorderly arranged and the structure is loose.Compared with the model group,the swelling of neurons was relieved and was arranged more neatly of Meiduoba group,and that of the Shaoyao Gancao Decoction group was more significantly improved.Conclusion:Shaoyao Gancao Decoction can effectively improve the neurotransmitter levels in the brain of rats with Parkinson′s disease,relieve muscle rigidity and improve the autonomic activity of PD rats.
引文
[1]檀国祥,许啟伍,丁婷,等.早期帕金森病病人嗅觉障碍的相关性分析[J].蚌埠医学院学报,2017,42(3):339-341.
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[5]蔡悦萍,张贵君,朱广伟,等.配伍比例及配伍组分对芍药甘草汤中9种药效组分的影响[J].药物分析杂志,2015,35(10):1770-1776.
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[8]王丹,许莹.在左旋多巴治疗原发性帕金森病致“开-关”现象的控制中卡比多巴/左旋多巴的应用及效果[J].中国临床研究,2017,30(4):514-517.
[9]李雪,姜立刚.多巴胺受体激动剂在帕金森病治疗中的剂量与疗效关系探讨[J].国际老年医学杂志,2016,37(4):145-149.
[10]黄志兰,赵杨.中医治疗帕金森病的现状与展望[J].中西医结合心脑血管病杂志,2013,11(1):81-83.
[11]汪萌,闫永红,邹慧琴,等.芍药甘草汤功能与药效组分对应性研究[J].国际药学研究杂志,2015,42(1):101-106.
[12]谢兰兰,陈思思,王燕鸿,等.芍药甘草汤加味联合运动训练治疗脑卒中后偏瘫肘关节屈曲痉挛疗效观察[J].现代中西医结合杂志,2016,25(7):750-752.
[13]张春双,蔡靖.芍药甘草汤结合运动治疗脑卒中后肌痉挛临床疗效分析[J].亚太传统医药,2015,11(13):131-132.
[14]刘皈阳,闫旭,李外,等.白芍不同炮制品中芍药苷含量及镇痛作用[J].解放军药学学报,2015,21(12):167-169.
[15]宋扬,赵昱,曾凡荣,等.大鼠脊髓内大麻素CB2受体在芍药苷拮抗吗啡镇痛耐受中的作用[J].神经解剖学杂志,2016,32(5):635-640.
[16]薛梅,穆道周,黄熙.芍药苷对抑郁大鼠海马组织形态及BDNF水平的影响[J].南京中医药大学学报,2016,32(5):439-441.
[17]周丽芳,彭慧云,欧阳文献,等.芍药苷对实验性大鼠脓毒症肝损伤的保护作用[J].医学临床研究,2016,33(5):861-864.
[18]周楠楠,朱燃,赵雪梅,等.天麻素、黄芪总皂苷和芍药苷对阿尔茨海默病模型小鼠脑内β-淀粉样多肽表达的影响及其机制[J].中华病理学杂志,2016,45(11):780-785.
[19]朱广伟,张贵君,王晶娟,等.单因素配伍剂量对经方芍药甘草汤药效组分的影响[J].实用药物与临床,2015,18(2):168-173.
[20]李鸿飞,卿德刚,张娟,等.甘草渣中总黄酮清除·OH自由基能力的研究[J].新疆医科大学学报,2015,38(2):182-183.
[21]赵雨坤,李立,刘学,等.基于系统药理学探索甘草有效成分甘草甜素的药理作用机制[J].中国中药杂志,2016,41(10):1916-1920.
[2]陈文广,郭刚.高龄帕金森病患者临床特征分析[J].西部医学,2015,27(6):896-899.
[3]刘佳,段春礼,杨慧.帕金森病发病机制与治疗研究进展[J].生理科学进展,2015,46(3):163-169.
[4]王丽云,刘丽星,吕海军,等.抗帕金森病药物的研究进展[J].中国药房,2017,28(8):1143-1149.
[5]蔡悦萍,张贵君,朱广伟,等.配伍比例及配伍组分对芍药甘草汤中9种药效组分的影响[J].药物分析杂志,2015,35(10):1770-1776.
[6]张雪,张雯,杜立达,等.抗帕金森病药物及其作用靶点研究进展[J].国际药学研究杂志,2016,43(1):87-96.
[7]李晋,贺敬敬,易蕊,等.左旋多巴/卡比多巴联合恩他卡朋治疗帕金森病的临床研究[J].现代生物医学进展,2016,16(3):504-506.
[8]王丹,许莹.在左旋多巴治疗原发性帕金森病致“开-关”现象的控制中卡比多巴/左旋多巴的应用及效果[J].中国临床研究,2017,30(4):514-517.
[9]李雪,姜立刚.多巴胺受体激动剂在帕金森病治疗中的剂量与疗效关系探讨[J].国际老年医学杂志,2016,37(4):145-149.
[10]黄志兰,赵杨.中医治疗帕金森病的现状与展望[J].中西医结合心脑血管病杂志,2013,11(1):81-83.
[11]汪萌,闫永红,邹慧琴,等.芍药甘草汤功能与药效组分对应性研究[J].国际药学研究杂志,2015,42(1):101-106.
[12]谢兰兰,陈思思,王燕鸿,等.芍药甘草汤加味联合运动训练治疗脑卒中后偏瘫肘关节屈曲痉挛疗效观察[J].现代中西医结合杂志,2016,25(7):750-752.
[13]张春双,蔡靖.芍药甘草汤结合运动治疗脑卒中后肌痉挛临床疗效分析[J].亚太传统医药,2015,11(13):131-132.
[14]刘皈阳,闫旭,李外,等.白芍不同炮制品中芍药苷含量及镇痛作用[J].解放军药学学报,2015,21(12):167-169.
[15]宋扬,赵昱,曾凡荣,等.大鼠脊髓内大麻素CB2受体在芍药苷拮抗吗啡镇痛耐受中的作用[J].神经解剖学杂志,2016,32(5):635-640.
[16]薛梅,穆道周,黄熙.芍药苷对抑郁大鼠海马组织形态及BDNF水平的影响[J].南京中医药大学学报,2016,32(5):439-441.
[17]周丽芳,彭慧云,欧阳文献,等.芍药苷对实验性大鼠脓毒症肝损伤的保护作用[J].医学临床研究,2016,33(5):861-864.
[18]周楠楠,朱燃,赵雪梅,等.天麻素、黄芪总皂苷和芍药苷对阿尔茨海默病模型小鼠脑内β-淀粉样多肽表达的影响及其机制[J].中华病理学杂志,2016,45(11):780-785.
[19]朱广伟,张贵君,王晶娟,等.单因素配伍剂量对经方芍药甘草汤药效组分的影响[J].实用药物与临床,2015,18(2):168-173.
[20]李鸿飞,卿德刚,张娟,等.甘草渣中总黄酮清除·OH自由基能力的研究[J].新疆医科大学学报,2015,38(2):182-183.
[21]赵雨坤,李立,刘学,等.基于系统药理学探索甘草有效成分甘草甜素的药理作用机制[J].中国中药杂志,2016,41(10):1916-1920.