摘要
目的:研究甜叶菊糖苷的抗抑郁作用及其对小鼠脑和脾脏组织中白蛋白D位点结合蛋白(DBP)、γ-氨基丁酸B2受体(Gabbr2)和P物质蛋白(SP)表达的影响。方法:将♂BALB/c小鼠随机分为5组,即正常组、模型组、阳性对照组(氟西汀,30mg/kg)、甜菊糖苷6.25 mg/kg、12.5 mg/kg组,每组12只。正常组和模型组动物给予等体积的生理盐水,其他组动物给予相应药物,每天灌胃给药1次,共治疗7天。采用糖水偏好、强迫游泳实验测定小鼠的行为学指标;采用高效液相荧光法测定小鼠脑组织中谷氨酸(Glu)、γ-氨基丁酸(GABA)、多巴胺(DA)和5-羟色胺(5-HT)的含量;采用Western blot法测定小鼠脑及脾脏组织中DBP、Gabbr2和SP蛋白的表达。结果:与正常组比较,模型组糖水偏好率、GABA、DA、5HT含量明显降低,游泳不动时间、Glu含量增高,脑组织中DBP、Gabbr2、SP及脾组织DBP、SP蛋白下调。与模型组比较,甜叶菊糖苷能剂量依赖性地增加抑郁小鼠的糖水偏好率,减少强迫游泳的不动时间;甜叶菊糖苷6.25 mg/kg组Glu的含量明显降低,GABA、DA和5-HT的含量明显升高,同时明显上调抑郁小鼠脑组织中DBP、Gabbr2和SP蛋白的表达及脾脏组织中DBP与SP蛋白的表达,而12.5 mg/kg作用不明显。结论:6.25 mg/kg甜叶菊糖苷可有效改善抑郁症状,其抗抑郁机制可能与调控脑和脾脏组织中的DBP、Gabbr2与SP蛋白的表达有关。
Objective:To study the antidepressant effect of stevioside and its effect on the expression of albumin D-site binding protein(DBP),γ-aminobutyric acid B2 receptor(GAbbr2)and substance P(SP)in the mouse brain and the spleen.Methods:♂BALB/c mice were randomly divided into 5 groups:the control group,the model group,the positive control group(fluoxetine,30 mg/kg)and stevioside groups(6.25 mg/kg and 12.5 mg/kg),12 in each group.Animals in the group and the model group were given normal saline,and other groups of animals were intragastrically administered with corresponding drugs,once a day for 7 consecutive days.Sucrose preference and forced swimming tests were used to determine behavioral indicators in mice.The contents of glutamic acid(Glu),γ-aminobutyric acid(GABA),dopamine(DA)and serotonin(5-HT)in brain tissues were determined by high performance liquid chromatography.The expression levels of DBP,Gabbr2 and SP protein in brains and spleens were determined by Western blot.Results:Compared with the control group,the sucrose preference rate,the contents of GABA,DA and5 HT,swimming time and Glu level were increased,the levels of DBP、Gabbr2、SP in brains and DBP、SP in spleens were decreased.Compared with the model group,Stevioside significantly increased the sucrose preference rate and reduced the forced-swimming time in depressed mice,in a dose-dependent manner.In 6.25 mg/kg stevioside group,the level of Glu was decreased,the contents of GABA,DA and 5-HT were significantly increased.In addition,the expressions of DBP、Gabbr2 and SP proteins in brain tissues and the expression of DBP and SP proteins in spleen tissues were significantly up regulated.In 12.5 mg/kg stevioside group,no significant effect was observed.Conclusion:6.25 mg/kg stevioside can effectively improve the depression symptoms,which may be related to regulating the expression of DBP,Gabbr2 and SP protein in brain and spleen tissues.
作者
胡雨
黄锋
詹合琴
韩旭萌
焦明丽
Hu Yu;Huang Feng;Zhan Heqin;Han Xumeng;Jiao Mingli(School of Pharmacy,Xinxiang Medical University,Xinxiang 453003)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2019年第4期84-90,共7页
Pharmacology and Clinics of Chinese Materia Medica
基金
河南省自然科学基金(编号:162300410219)