熄风静宁颗粒对Tourette综合征模型大鼠行为活动及脑纹状体多巴胺递质的影响
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摘要
目的观察熄风静宁颗粒对Tourette综合征(TS)模型大鼠行为活动,及脑纹状体多巴胺(DA)、血清高香草酸(HVA)含量的影响。方法 Wistar雄性大鼠42只随机分为正常组、模型组、氟哌啶醇组、熄风静宁颗粒低剂量组[1.2 g/(kg·d)]、熄风静宁颗粒中剂量组[2.4 g/(kg·d)]、熄风静宁颗粒高剂量组[4.8 g/(kg·d)],每组7只,采用亚氨基二丙腈(IDPN)腹腔注射建立TS大鼠模型,造模后,正常组和模型组给予蒸馏水灌胃,其余4组分别予相应药物灌胃,连续给药6周后,观察比较各组大鼠的行为活动,采用酶联免疫吸附法(ELISA)检测小鼠纹状体内DA、血清HVA含量。结果熄风静宁颗粒中、高剂量组及氟哌啶醇组可以减轻TS模型大鼠抽动行为,与模型组比较均存在明显差异。模型组大鼠脑纹状DA含量明显低于正常组(P<0.05)。熄风静宁颗粒中、高剂量组能增加大鼠脑纹状体DA含量,与模型组比较差异具有统计学意义(P<0.05);熄风静宁颗粒高剂量组大鼠血清HVA含量较低剂量组偏高,差异具有统计学意义(P<0.05)。结论熄风静宁颗粒可以降低中枢神经兴奋性,其治疗作用可能是通过调节突触后多巴胺受体敏感性或其他的药物作用靶位实现。
Objective: To observe effects of Xifeng Jingning Decoction on the behavior,content of striatum dopamine(DA),and homovanillic acid(HVA) in rats model of Tourette syndrome. Methods: Male Wistar rats(n= 42) were randomly divided into the blank group,the model group,the haloperidol group,low-dose [1.2 g/(kg·d)] of Xifeng Jingning Decoction group,middle-dose [(2.4 g/(kg·d)] of Xifeng Jingning Decoction group,and high-dose [(4.8 g/(kg·d)] of Xifeng Jingning Decoction group(each n = 7). The Tourette syndrome model was established in rats by intraperitoneal injection of iminodipropionitrile(IDPN). After modeling,the blank group and the model group were given normal saline solution intragastrically and other groups were given relevant medicines for 6 weeks. The behavior was compared in all groups,and the content of striatum DA and HVA were detected by using enzymelinked immunosorbent assay(ELISA). Results: Middle-dose group and high-dose group of Xifeng Jingning Decoction,and haloperidol group lessened the stereotyped behavior in rats model of Tourette syndrome with a significance difference,compared with the model group. The content of DA decreased in model group compared with that in blank group(P < 0.05). Compared with the model group,there were differences in the content of striatum DA in middle-dose and high-dose of Xifeng Jingning Decoction groups(P < 0.05). The content of HVA increased in high-dose of Xifeng Jingning Decoction group,compared with that in low-dose of Xifeng Jingning Decoction,with a significance difference(P < 0.05). Conclution: Xifeng Jingning Decoction can reduce the excitability of central nerve. The therapeutic effect of Xifeng Jingning Decoction may be implemented regulating the sensitivity of postsynaptic dopamine receptors or other drug targets.
Objective: To observe effects of Xifeng Jingning Decoction on the behavior,content of striatum dopamine(DA),and homovanillic acid(HVA) in rats model of Tourette syndrome. Methods: Male Wistar rats(n= 42) were randomly divided into the blank group,the model group,the haloperidol group,low-dose [1.2 g/(kg·d)] of Xifeng Jingning Decoction group,middle-dose [(2.4 g/(kg·d)] of Xifeng Jingning Decoction group,and high-dose [(4.8 g/(kg·d)] of Xifeng Jingning Decoction group(each n = 7). The Tourette syndrome model was established in rats by intraperitoneal injection of iminodipropionitrile(IDPN). After modeling,the blank group and the model group were given normal saline solution intragastrically and other groups were given relevant medicines for 6 weeks. The behavior was compared in all groups,and the content of striatum DA and HVA were detected by using enzymelinked immunosorbent assay(ELISA). Results: Middle-dose group and high-dose group of Xifeng Jingning Decoction,and haloperidol group lessened the stereotyped behavior in rats model of Tourette syndrome with a significance difference,compared with the model group. The content of DA decreased in model group compared with that in blank group(P < 0.05). Compared with the model group,there were differences in the content of striatum DA in middle-dose and high-dose of Xifeng Jingning Decoction groups(P < 0.05). The content of HVA increased in high-dose of Xifeng Jingning Decoction group,compared with that in low-dose of Xifeng Jingning Decoction,with a significance difference(P < 0.05). Conclution: Xifeng Jingning Decoction can reduce the excitability of central nerve. The therapeutic effect of Xifeng Jingning Decoction may be implemented regulating the sensitivity of postsynaptic dopamine receptors or other drug targets.
引文
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[11]王道涵,王素梅,卫利芳.健脾止动汤对多发性抽动症模型小鼠纹状体多巴胺及受体含量的影响[J]﹒北京中医药大学学报,2012,35(7):452-455﹒
[12]车立纯.抽动障碍动物模型的比较研究[D]﹒青岛:青岛大学,2014.
[13]陈祺.宣桂琪名老中医治疗小儿抽动-秽语综合征[J].中医药学报,2009,37(3):43-45.
[14]赖东兰,李宜瑞.李宜瑞教授治疗儿童抽动-秽语综合征经验述要[J].中医药学刊,2004,22(7):1176.
[15]陈要金.郑健治疗小儿抽动-秽语综合征经验[J].中医药临床杂志,2009,21(5):390-391.
[16]于作洋,王基鑫﹒熄风静宁汤治疗小儿多发性抽动症临床观察[J]﹒中日友好医院学报,2006,20(2):124﹒
[2]Wong DF,Bras JR,Singer HS﹒Mechanisms of dopaminergic and serotonergic neurotransmission in tourette syndrome:Clues from an In Vi Vo neurochem istry study with PET[J].Neuropsychopharmacology,2008,33:1239-1251.
[3]冯刚,马丙祥,李华伟.熄风静宁汤加减治疗小儿多发性抽动症63例临床总结[J].四川中医,2005,23(5):64-65.
[4]王俊宏,肖和印,尹丹.熄风静宁冲剂治疗抽动-秽语综合征的临床研究[J].北京中医药大学学报,2002,25(5):67-68.
[5]Napier TC,Istre ED﹒Methamphetamine-Induced sensitization includes a functional upregulation of ventral pallidal 5-HT2A/2C receptors[J]﹒Synapse,2008,62:14-21﹒
[6]刘智胜﹒小儿多发性抽动症[M]﹒北京:人民卫生出版社,2002:32-74﹒
[7]Matt JN,Elaine CJ,Robert TW.Identification and characterization of ANKK1:a novel kinase gene closely linked to DRD2on chromosome band 11q23.1[J].Hum Mutat,2004,23:540-545.
[8]Cohen DJ,Shaywitz BA,Young JG,et al.Central biogenic amine netabolism in children with the syndrome of chronic motiple tics of Gilles de la Tourrette′s syndrome:norepinephkine,serotonin and dopamine[J].J Am acad child psychiatry,1979,19:320.
[9]Butler IJ,Koslow SH,Seifers WEJ,et al.Biogenic amine metabolism in Tourrette′s syndrome[J].Ann neurol,1979,6:37-39.
[10]Diamond BI,Reyes MG,Borision R.A new animal model for Tourctte syndrome[J].Adv Neural,1982,35:221-225.
[11]王道涵,王素梅,卫利芳.健脾止动汤对多发性抽动症模型小鼠纹状体多巴胺及受体含量的影响[J]﹒北京中医药大学学报,2012,35(7):452-455﹒
[12]车立纯.抽动障碍动物模型的比较研究[D]﹒青岛:青岛大学,2014.
[13]陈祺.宣桂琪名老中医治疗小儿抽动-秽语综合征[J].中医药学报,2009,37(3):43-45.
[14]赖东兰,李宜瑞.李宜瑞教授治疗儿童抽动-秽语综合征经验述要[J].中医药学刊,2004,22(7):1176.
[15]陈要金.郑健治疗小儿抽动-秽语综合征经验[J].中医药临床杂志,2009,21(5):390-391.
[16]于作洋,王基鑫﹒熄风静宁汤治疗小儿多发性抽动症临床观察[J]﹒中日友好医院学报,2006,20(2):124﹒