摘要
目的探讨天麻素对儿童多发性抽动症模型大鼠纹状体细胞外液5-羟色胺(5-HT)浓度的调节作用及其分子作用机制。方法将40只Wistar大鼠随机分为4组,即空白组、模型组、天麻素组、硫必利组,每组10只。除空白组予生理盐水5 mL/(kg·d)腹腔注射外,其余3组均予亚氨基二丙腈150 mg/(kg·d)腹腔注射制作多发性抽动症模型,造模共持续7 d。造模成功后,分别对大鼠进行药物干预。空白组、模型组均予生理盐水10 mL/(kg·d)灌胃,天麻素组予天麻素20 mg/(kg·d)灌胃,硫必利组予硫必利1 mg/(kg·d)灌胃,共持续8周。干预前后对大鼠的刻板行为进行行为学评价;收集各组脑脊液,分别应用微透析技术、高效液相色谱技术检测其纹状体细胞外液的5-HT、5-羟吲哚乙酸(5-HIAA)浓度;处死大鼠,快速分离出纹状体,采用蛋白质免疫印迹技术测定大鼠纹状体5-HT转运体(SERT)蛋白表达。结果与空白组比较,模型组刻板运动增多、细胞外液5-HT浓度降低、SERT蛋白表达灰度值升高(P均<0.05)。与模型组比较,干预4周天麻组和硫必利组刻板运动开始减少(P均<0.05);干预8周后天麻组纹状体细胞外液5-HT浓度升高、SERT蛋白表达降低(P均<0.05),硫必利组纹状体细胞外液5-HT浓度、SERT蛋白表达无明显变化(P均>0.05)。各组纹状体细胞外液5-HIAA浓度比较差异无统计学意义(P均>0.05)。结论天麻素具有与硫必利相似的抑制儿童多发性抽动症模型大鼠刻板运动的作用,其作用机制可能与调节5-HT浓度、SERT蛋白表达量有关。
Objective To evaluate the regulating effect of gastrodin(GAS)on striatal extracellular 5-hydroxytrypta⁃minen(5-HT)concentration in the rat models of tic disorders(TD)of children,and to explore the molecular mechanism.Methods Forty male Wistar rats were randomly divided into four groups:the control group,TD model group,GAS group and tiapride group.Except for the control group,in which rats were intraperitoneally injected with normal saline(0.9%)(5 mL/kg),rats in the other three groups were injected with 3,3’-iminodipropionitrile(IDPN)(150 mg/kg)for 7 days to develop the rats models of TD.After that,the related rats were treated respectively by oral gavage with normal saline at 10 mL/kg(the control group and the TD model group),GAS at 10 mg/kg(the GAS group),and tiapride at 1.0 mg/kg(the tiapride group)once a day,for 8 weeks.Before and after the treatment,we studied the alterations in the stereotyped abnormalities of the rats on a weekly basis.The regulating effects of GAS on striatal extracellular 5-HT and 5-hydroxyindole acetic acid(5-HIAA)content were evaluated by intracerebral microdialysis and follow-up high-perfor⁃mance liquid chromatography(HPLC).The correlated changes in SERT protein expression was further determined by Western blotting after the rats were sacrificed and the striatum tissues were dissected.Results Compared with the con⁃trol group,the stereotyped movement of rats increased,the concentration of extracellular 5-HT decreased,and the gray value of SERT protein expression increased in the model group(all P<0.05).Compared with the TD model group,the stereotyped movement of rats decrease in both the GAS group and the tiapride group after 4 weeks of intervention(both P<0.05);after 8 weeks of intervention,the striatal extracellular 5-HT concentration increased and SERT protein expression decreased in the GAS group(all P<0.05),while the striatal extracellular 5-HT concentration and SERT protein expres⁃sion did not change significantly in the tiapride group(all P>0.05).There was no significant difference in the striatal ex⁃tracellular 5-HT concentration between groups(P>0.05).Conclusion Similar to tiapride,GAS could make a signifi⁃cant improvement on stereotyped behavioral abnormalities of TD rats,and the mechanism of action may be related to the regulation of 5-HT concentration and SERT protein expression.
作者
董博
孔敏
宋莹
姜宁
李慧
张艳秋
张峰
DONG Bo;KONG Min;SONG Ying;JIANG Ning;LI Hui;ZHANG Yanqiu;ZHANG Feng(Department of Acupuncture and Massage,Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University,Jinan 250014,China;不详)
出处
《山东医药》
CAS
2023年第16期5-8,共4页
Shandong Medical Journal
基金
山东省中医药科技发展计划项目(2017-291)
山东省医药卫生科技发展计划项目(2018WS314)。
