健脾止动汤通过纹状体内多巴胺系统治疗多发性抽动症大鼠的机制研究  

Effect of Jianpi Zhidong Decoction on rats with Tourette syndrome through intrastriatal dopamine system

作　　者：腾尚宇 薛小娜[2] 陈自佳[2] 李钰萍 刘晓芳[2] TENG Shangyu;XUE Xiaona;CHEN Zijia;LI Yuping;LIU Xiaofang(The Second School of Clinical Medicine Affiliated to Beijing University of Chinese Medicine,Beijing 100078,China;Department of Pediatrics,Dongfang Hospital Affiliated to Beijing University of Chinese Medicine,Beijing 100078)

机构地区：[1]北京中医药大学第二临床医学院,北京100078 [2]北京中医药大学东方医院儿科,北京100078

出　　处：《北京中医药》2024年第9期1028-1033,共6页Beijing Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金青年基金项目(82004422,82205191);儿科专委会青年医师创新发展项目(2018-JYBZZ-JS127)。

摘　　要：目的观察健脾止动汤通过纹状体内多巴胺(DA)囊泡循环对多发性抽动症(TS)模型大鼠的影响。方法将42只大鼠按照完全随机分组法分为空白组10只、造模组32只。造模组给予腹腔注射亚氨基二丙腈(IDPN)制备模型,空白组给予腹腔注射等体积生理盐水,均1次/d,连续7 d。将造模成功的30只大鼠按照完全随机分组法分为模型组、健脾止动汤组(中药组)、泰必利组,每组10只。中药组给予健脾止动汤免煎颗粒1.6 g/100 g灌胃,泰必利组给予泰必利混悬液2.1 mg/100 g灌胃,空白组、模型组均给予1 mL/100 g生理盐水灌胃,1次/d,连续4周。对比各组第1、8、15、22、29、36天刻板运动评分,纹状体内酪氨酸羟化酶(TH)、多巴胺转运蛋白(DAT)、Ⅱ型囊泡单胺转移体(VMAT2)、α突触核蛋白(α-syn)表达。结果第8天造模结束时,与空白组比较,模型组、泰必利组刻板行为评分高(P<0.05);第22天起,与模型组比较,中药组、泰必利组刻板行为评分低(P<0.05),中药组与泰必利组各时间点比较差异均无统计学意义(P>0.05)。与第1天比较,第8天与第15天模型组、中药组、泰必利组刻板行为评分均升高(P<0.05);与第8天比较,第29天起中药组、泰必利组刻板行为评分均降低(P<0.05)。与空白组比较,模型组纹状体内TH蛋白表达高、DAT蛋白表达低(P<0.05)。与模型组比较,中药组、泰必利组TH蛋白表达低(P<0.05),中药组DAT蛋白表达高(P<0.05)。与空白组比较,模型组纹状体内α-syn蛋白表达高、VMAT2蛋白表达低(P<0.05)。与模型组比较,中药组、泰必利组α-syn蛋白表达低,VMAT2蛋白表达高(P<0.05)。结论健脾止动汤通过调节TS模型大鼠纹状体内DA的囊泡循环,抑制α-syn过度释放,提高DAT及VMAT2表达,降低大脑突触间隙内的DA含量,发挥抗抽动作用。Objective To observe the effect of Jianpi Zhidong Decoction on intrastriatal dopamine(DA)vesicle circulation of Tourette syndrome(TS)model rats.Methods Forty-two rats were randomly divided into a blank group(n=10)and an experimental group(n=32)using a complete randomization method.The experimental group was given intraperitoneal injections of iminodipropionitrile(IDPN)to establish the model,while the blank group was given intraperitoneal injections of an equal volume of saline,once daily for 7 consecutive days for both groups.The 30 successfully modeled rats were then randomly divided into a model group,a Jianpi Zhidong Decoction group(TCM group),and a Tiapride group using a complete randomization method,with 10 rats in each group.The TCM group was given Jianpi Zhidong Decoction granules at 1.6 g/100 g by gavage,and the Tiapride group was given Tiapride suspension at 2.1 mg/100 g by gavage.The blank and model groups were both given saline at 1 mL/100 g by gavage once daily for 4 consecutive weeks.Stereotyped behavior scores in all groups were compared on days 1,8,15,22,29,and 36.The expression of tyrosine hydroxylase(TH),dopamine transporter(DAT),vesicular monoamine transporter 2(VMAT2),andα-synuclein(α-syn)in the striatum was also measured and compared.Results By day 8,at the end of modeling,the stereotyped behavior scores in the model group and the Tiapride group were higher than those in the blank group(P<0.05).From day 22 onward,the stereotyped behavior scores in the TCM and the Tiapride groups were lower than those in the model group(P<0.05),with no statistically significant difference between the TCM and the Tiapride groups at any time point(P>0.05).Compared with the stereotyped behavior scores on day 1,those in the model,TCM,and Tiapride groups increased on days 8 and 15(P<0.05).However,compared with the stereotyped behavior scores on day 8,those in the TCM and Tiapride groups decreased from day 29 onward(P<0.05).Compared with the blank group,the model group had higher TH protein expression and lower DAT

关 键 词：健脾止动汤 多发性抽动症 纹状体 酪氨酸羟化酶 多巴胺转运蛋白 Ⅱ型囊泡单胺转移体 Α突触核蛋白 大鼠 

分 类 号：R285.5[医药卫生—中药学]