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
腾尚宇,女,25岁,硕士研究生。研究方向:中医儿科学。
刘晓芳,E-mail:liuxiaofang1226@163.com
纸质出版日期:2024-09-25,
收稿日期:2023-12-22,
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腾尚宇,薛小娜,陈自佳,等.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[J].北京中医药,2024,43(9):1028-1033.
TENG Shangyu,XUE Xiaona,CHEN Zijia,et al.Effect of Jianpi Zhidong Decoction on rats with Tourette syndrome through intrastriatal dopamine system[J]. Beijing Journal of Traditional Chinese Medicine,2024,43(09):1028-1033.
腾尚宇,薛小娜,陈自佳,等.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[J].北京中医药,2024,43(9):1028-1033. DOI: 10.16025/j.1674-1307.2024.09.014.
TENG Shangyu,XUE Xiaona,CHEN Zijia,et al.Effect of Jianpi Zhidong Decoction on rats with Tourette syndrome through intrastriatal dopamine system[J]. Beijing Journal of Traditional Chinese Medicine,2024,43(09):1028-1033. DOI: 10.16025/j.1674-1307.2024.09.014.
目的
2
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
2
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
2
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
2
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
2
To observe the effect of Jianpi Zhidong Decoction on intrastriatal dopamine (DA) vesicle circulation of Tourette syndrome (TS) model rats.
Methods
2
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), and α-synuclein (α-syn) in the striatum was also measured and compared.
Results
2
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 sco
res 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 protein expression in the striatum (
P
<
0.05). Compared with the model group, both the TCM and the Tiapride groups had lower TH protein expression (
P
<
0.05), while the TCM group had higher DAT protein expression (
P
<
0.05). Additionally, compared with the blank group, the model group had higher α-syn protein expression and lower VMAT2 protein expression in the striatum (
P
<
0.05). Compared with the model group, both the TCM and the Tiapride groups had lower α-syn protein expression and higher VMAT2 protein expression (
P
<
0.05).
Conclusion
2
Jianpi Zhidong Decoction exerts an anti-tic effect by regulating DA vesicle circulation in the striatum of TS model rats, inhibiting excessive α-syn release, increasing the expression of DAT and VMAT2, and reducing DA content in the synaptic cleft of the brain.
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
Jianpi Zhidong DecoctionTourette syndromecorpus striatumtyrosine hydroxylasedopamine transportervesicular monoamine transporter 2α-synucleinrat
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