升清降浊制动颗粒对多发性抽动症模型大鼠脑组织内GABA、Glu、ASP含量影响
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摘要
目的:观察升清降浊制动颗粒对多发性抽动症行为学及脑组织内GABA、Glu、ASP含量影响,探讨升清降浊制动颗粒治疗多发性抽动症的作用机制。方法:将70只雄性SD大鼠随机分为空白对照组、模型组、氟哌啶醇0.2mg/kg组、升清降浊制动颗粒258mg/kg、129mg/kg组5组,每组14只,除空白对照组注射生理盐水,其余各组腹腔注射IDPN 150mg/kg建立TS大鼠模型,药物干预3周后,断头取脑,采用高效液相色谱-四级杆离子阱串联质谱仪检测脑组织内GABA、Glu、ASP的含量。结果:在实验中5只始终未达到造模标准,死亡大鼠6只,最终59只大鼠参与统计分析,治疗后氟哌啶醇0.2mg/kg组、升清降浊颗粒258mg/kg、129mg/kg组,与模型组比较,运动行为及刻板行为明显减少,中央格停留时间缩短、跨格次数显著减少,攀网时间延长,脑组织GABA含量显著升高,Glu、ASP含量显著降低。结论:升清降浊制动颗粒能够改善大鼠运动行为、刻板行为、动物中枢兴奋性及协调性,其作用机制可能是通过调节脑内兴奋性氨基酸Glu、ASP与抑制性氨基酸GABA平衡实现的。
Objective:To investigate the action mechanism of Granules via Ascending Clear qi and Descending Turbid qi(GACDT) on Tourette Syndrome(TS).Methods:70 healthy male Sprague-Dawley(SD) rats were randomly divided into the control group,the model group,Haloperidol group(0.2 mg/kg),high dose of GACDT-group(258 mg/kg) and low dose of GACDT group(129 mg/kg),14 rats in each group.Rats in the control group were treated with intraperitoneal injection of saline,while rats in other groups were intraperitoneally injected with 3,3,-iminodipropionitrile(IDPN) at a dose of 150 mg/kg.After 3 weeks' treatment,brain tissues were collected to determine contents of GABA、Glu、ASP through High performance liquid chromatography four stage rod ion trap tandem mass spectrometry(HPLC-MS/MS Q-TRAP).Results:In the experiment,5 rats were failed in model establishment,6 rats died,and finally 59 rats were used in statistical analysis.Compared with the control group,rats in Haloperidol group(0.2 mg/kg),high dose of GACDT group(258 mg/kg) and low dose of GACDT group(129 mg/kg) showed the significant reduction in motor behavior and stereotyped behavior.Also it showed that the central compartment retention time in those groups was shortened,cross-grid frequency was reduced,climbing time was extended,GABA contents were increased and contents of Glu and ASP in brain tissues were decreased.Conclusion:GACDT can improve the motor behavior,stereotypes,animal central excitability and coordination.Its mechanism may be related to regulating the balance of excitatory amino acids Glu,ASP and inhibitory amino acid GABA in the brain.
Objective:To investigate the action mechanism of Granules via Ascending Clear qi and Descending Turbid qi(GACDT) on Tourette Syndrome(TS).Methods:70 healthy male Sprague-Dawley(SD) rats were randomly divided into the control group,the model group,Haloperidol group(0.2 mg/kg),high dose of GACDT-group(258 mg/kg) and low dose of GACDT group(129 mg/kg),14 rats in each group.Rats in the control group were treated with intraperitoneal injection of saline,while rats in other groups were intraperitoneally injected with 3,3,-iminodipropionitrile(IDPN) at a dose of 150 mg/kg.After 3 weeks' treatment,brain tissues were collected to determine contents of GABA、Glu、ASP through High performance liquid chromatography four stage rod ion trap tandem mass spectrometry(HPLC-MS/MS Q-TRAP).Results:In the experiment,5 rats were failed in model establishment,6 rats died,and finally 59 rats were used in statistical analysis.Compared with the control group,rats in Haloperidol group(0.2 mg/kg),high dose of GACDT group(258 mg/kg) and low dose of GACDT group(129 mg/kg) showed the significant reduction in motor behavior and stereotyped behavior.Also it showed that the central compartment retention time in those groups was shortened,cross-grid frequency was reduced,climbing time was extended,GABA contents were increased and contents of Glu and ASP in brain tissues were decreased.Conclusion:GACDT can improve the motor behavior,stereotypes,animal central excitability and coordination.Its mechanism may be related to regulating the balance of excitatory amino acids Glu,ASP and inhibitory amino acid GABA in the brain.
引文
1张雯,崔霞,于文静,等."阴阳平衡"与多发性抽动症氨基酸类神经递质调控的相关性.中华中医药学刊,2015;33(2)∶275~277
2郑宏,郑攀,郑启仲.郑启仲运用升降散治疗儿科疾病经验.中华中医药杂志,2014;29(6)∶1864~1866
3郑宏,郑攀,郑启仲.郑启仲治疗小儿多发性抽动症经验.中医杂志,2012;53(3)∶95~197
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5鱼达,李辉,姜骊.实验动物随机分组的计算机程序处理.实验动物科学,2011;28(01)∶25~27
6杜淑娟,彭贝如,程树军,等.抽动-秽语综合症动物模型的建立和评价.中国比较医学杂志,2010;20(3)∶23~25
7张如意,张丽,艾厚喜,等.金童颗粒治疗拟抽动秽语综合征模型大鼠的药理机制研究.中国康复理论与实践,2010;16(10)∶910~912
8 Cath D C,Hedderly T,Ludolph A G,et al.European clinical guidelines for Tourette Syndrome and other tic disorders.Eur Child Adolesc Psychiatry,2011;20(10)∶155~171
9 Giraldo B O,David M,Sánchez Y,et al.Prevalence of Tics Among 6-to 12-Year-Old.Schoolchildren in the Itagui Municipality,Colombia,in 2010.Journal of Child Neurology.2013;23(1)∶385~386
10 Zavadenko N N,Doronina O B,Nesterovsky Y E.Chronic tics and Tourette syndrome in children and adolescents:diagnostic and treatment characteristics.Zh Nevrol Psikhiatr Im S SKorsakova.2015;115(1)∶102~109
11雷婧,邓雄,宋冶,等.抽动秽语综合症的进展.内科理论与实践,2010;5(5)∶383~389
12 Singer H S,Morris C,Grados M.Glutamatergic modulatory therapy for Tourette syndrome.Med Hypotheses,2009;74(5)∶862~867
13侯广舜,李安源,赵林,等.宁动颗粒对抽动秽语综合征模型大鼠纹状体5-羟色胺系统的影响.上海中医药杂志,2014;36(11)∶74~77
14解莹晶,朱先康.小儿多发性抽动症的相关实验研究进展.成都中医药大学学报,2014;37(1)∶121~124
15 Kanaan A S,Gerasch S,Garcíagarcía I,et al.Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome.Brain A Journal of Neurology,2017;140(1)∶218~234
16 Puts N A,Harris A D,Crocetti D,et al.Reduced GABAergic inhibition and abnormal sensory symptoms in children with Tourette syndrome.Journal of Neurophysiology,2015;114(2)∶808
2郑宏,郑攀,郑启仲.郑启仲运用升降散治疗儿科疾病经验.中华中医药杂志,2014;29(6)∶1864~1866
3郑宏,郑攀,郑启仲.郑启仲治疗小儿多发性抽动症经验.中医杂志,2012;53(3)∶95~197
4郑宏,高国财,郑攀,等.升清降浊制动颗粒治疗多发性抽动症痰热动风证临床研究.中医学报,2015;30(11)∶1650~1652
5鱼达,李辉,姜骊.实验动物随机分组的计算机程序处理.实验动物科学,2011;28(01)∶25~27
6杜淑娟,彭贝如,程树军,等.抽动-秽语综合症动物模型的建立和评价.中国比较医学杂志,2010;20(3)∶23~25
7张如意,张丽,艾厚喜,等.金童颗粒治疗拟抽动秽语综合征模型大鼠的药理机制研究.中国康复理论与实践,2010;16(10)∶910~912
8 Cath D C,Hedderly T,Ludolph A G,et al.European clinical guidelines for Tourette Syndrome and other tic disorders.Eur Child Adolesc Psychiatry,2011;20(10)∶155~171
9 Giraldo B O,David M,Sánchez Y,et al.Prevalence of Tics Among 6-to 12-Year-Old.Schoolchildren in the Itagui Municipality,Colombia,in 2010.Journal of Child Neurology.2013;23(1)∶385~386
10 Zavadenko N N,Doronina O B,Nesterovsky Y E.Chronic tics and Tourette syndrome in children and adolescents:diagnostic and treatment characteristics.Zh Nevrol Psikhiatr Im S SKorsakova.2015;115(1)∶102~109
11雷婧,邓雄,宋冶,等.抽动秽语综合症的进展.内科理论与实践,2010;5(5)∶383~389
12 Singer H S,Morris C,Grados M.Glutamatergic modulatory therapy for Tourette syndrome.Med Hypotheses,2009;74(5)∶862~867
13侯广舜,李安源,赵林,等.宁动颗粒对抽动秽语综合征模型大鼠纹状体5-羟色胺系统的影响.上海中医药杂志,2014;36(11)∶74~77
14解莹晶,朱先康.小儿多发性抽动症的相关实验研究进展.成都中医药大学学报,2014;37(1)∶121~124
15 Kanaan A S,Gerasch S,Garcíagarcía I,et al.Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome.Brain A Journal of Neurology,2017;140(1)∶218~234
16 Puts N A,Harris A D,Crocetti D,et al.Reduced GABAergic inhibition and abnormal sensory symptoms in children with Tourette syndrome.Journal of Neurophysiology,2015;114(2)∶808