摘要
目的:观察升清降浊制动颗粒对多发性抽动症(tourette syndrome,TS)模型大鼠纹状体内多巴胺(dopamine,DA)水平及多巴胺转运蛋白(dopamine transporter,DAT)、多巴胺D2受体(dopamine DZ receptor,DRD2) mRNA表达的影响。方法:将70只雄性SD大鼠随机分为空白对照组,模型组,氟哌啶醇组,升清降浊制动颗粒高剂量组、低剂量组,每组14只。采用3,3'-亚氨基二丙腈(3,3'-Iminodipropionitrile,IDPN)制备TS模型大鼠。从造模完成次日开始,空白对照组、模型组给予等体积生理盐水灌胃,氟哌啶醇组、升清降浊制动颗粒高剂量组、升清降浊制动颗粒低剂量组分别给予氟哌啶醇稀释液[200μg·kg-1]、升清降浊制动颗粒高剂量悬液[2. 58 mg·g-1]、升清降浊制动颗粒低剂量悬液[1. 29 mg·g-1]治疗,第21天结束后取材。采用高效液相色谱-四级杆离子阱串联质谱仪(HPLC-MS/MS Q-TRAP)检测纹状体中DA水平,RT-PCR检测纹状体中DAT、DRD2 mRNA表达水平。结果:与空白对照组比较,模型组运动行为评分、刻板行为评分均显著升高,差异均有统计学意义(P <0. 05)。与模型组比较,治疗后高剂量、低剂量升清降浊制动颗粒均能降低IDPN诱导的TS模型大鼠运动行为评分、刻板行为评分,差异均有统计学意义(P <0. 05)。与空白对照组比较,模型组DA水平显著降低,差异有统计学意义(P <0. 05)。与模型组比较,治疗后高剂量、低剂量升清降浊制动颗粒均能升高IDPN诱导的TS模型大鼠DA水平,差异均有统计学意义(P <0. 05)。与空白对照组比较,模型组DAT mRNA表达显著降低,DRD2mRNA表达显著升高,差异均有统计学意义(P <0. 05)。与模型组比较,治疗后高剂量、低剂量升清降浊制动颗粒均能升高DAT mRNA表达,降低DRD2 mRNA表达,差异均有统计学意义(P <0. 05);具有升高纹状体DA含量及上调DAT mRNA、下调DRD2 mRNA表达量的作用(P <0. 05)。结论:升清降浊制动颗粒能改善IDPN诱导的TS模型大鼠行为异常,其机制可能与升高纹状体DA水平及上调DAT mRNA表达、下调DRD2 mRNA表达有关。
Objective: To observe the effect of Shengqing Jiangzhuo Zhidong Granule on dopamine( DA) level,dopamine transporter( DAT) and dopamine D2 in striatum of rats with multiple Tourette syndrome( TS) and on the dopamine DZ receptor( DRD2)mRNA expression. Methods: Seventy male Sprague-Dawley rats were randomly divided into control group,model group,haloperidol group,high-dose group and low-dose group of Shengqing Jiangzhuo Zhidong Granules,with 14 rats in each group. TS model rats were prepared by using 3,3’-iminodipropionitrile( IDPN). From the next day after the modeling was completed,the blank control group and the model group were given an equal volume of normal saline. The haloperidol group,the high-dose group of Shengqing Jiangzhu brake granules,and the low-dose group of Shengqing turbidity brake granules were given separately: Haloperidol dilution[200 μg·kg-1],Shengqing Jiangzhuo Zhidong Granules high-dose suspension [2. 58 mg·g-1],Shengqing Jiangzhuo Zhidong Gradunes low-dose suspension [1. 29 mg·g-1]. Treatment lasted till the end of the 21 st day. The levels of DA in the striatum were detected by high performance liquid chromatography-quadrupole ion trap tandem mass spectrometry( HPLC-MS/MS QTRAP). The expression levels of DAT and DRD2 in the striatum were detected by RT-PCR. Results: Compared with that of the blank control group,the motor behavior scores and stereotype behavior scores of the model group were significantly increased( P <0. 05). Compared with that of the model group,the high-dose and low-dose Shengqing Jiangzhu Zhidong Granules group after treatment could reduce the motor behavior score and stereotype behavior score of the SD model induced by IDPN,and the difference was statistically significant( P < 0. 05). Compared with that of the blank control group,the DA level in the model group was significantly lower( P < 0. 05). Compared with that of the model group,the high-dose and low-dose Shengqing Jiangzhuo Zhidong Granules after treatment could increase the DA level of IDPN-induced TS model rats,and the difference was statistically significant( P < 0. 05). Compared with that of the blank control group,the expression of DAT was significantly decreased and the expression of DRD2 mRNA was significantly increased in the model group( P < 0. 05). Compared with that of the model group,high-dose and low-dose Shengqing Jiangzhuo Zhidong Grenules could increase DAT expression and decrease DRD2 mRNA expression,and the difference was statistically significant( P < 0. 05). Shengqing Jiangzhuo Zhidong Granules had the effect of increasing the content of DA in the striatum and up-regulating DAT and down-regulating the expression of DRD2 mRNA( P < 0. 05). Conclusion:Shengqing Jiangzhuo Zhidong Granules can improve the behavioral abnormality of IDPN-induced TS model rats,which may be related to the increase of striatum DA level,up-regulation of DAT expression and down-regulation of DRD2 mRNA expression.
作者
郑宏
高国财
梁瑞星
牛冬鹤
卢婷婷
张璠
冯斌
郑攀
ZHENG Hong;GAO Guocai;LIANG Ruixing;NIU Donghe;LU Tingting;ZHANG Fan;FENG Bin;ZHENG Pan(Henan University of Chinese Medicine,Zhengzhou Henan China 450046;Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital/Zhengzhou Children's Hospital,Zhengzhou Henan China 450082)
出处
《中医学报》
CAS
2018年第12期2374-2378,共5页
Acta Chinese Medicine
基金
全国名老中医药专家传承工作室建设项目{国中医药人教发[2011]41号}
河南省科技攻关项目(162102310099)
河南省基础与前沿技术研究计划项目(132300410380)
河南省中医药科学研究专项课题项目(2014ZY02036)
河南省中医药科学研究专项项目(2013ZY03012)
关键词
升清降浊制动颗粒
多发性抽动症
多巴胺
多巴胺转运体
多巴胺受体
大鼠
Shengqing Jiangzhuo Zhidong Granules
multiple tic disorder
dopamine
dopamine transporter
dopamine receptor
rat
作者简介
郑宏(1972-),女,河南清丰人,医学博士,教授,从事小儿神经遗传代谢病的中医药临床与研究;通信作者:郑攀(1977-),男,河南清丰人,医学博士,从事方剂作用机理与配伍规律研究。Email:drzhenghs@126.com
