百合多糖与黄芪多糖联用对慢性应激小鼠抑郁行为的影响及机制  

Effect and Mechanism of Lily Polysaccharide Combined with Astragalus Polysaccharide on Depressive Behavior in Chronic Stress Mice

作　　者：刘佳蕾 王宇亮[1] 赵宏[1] 沈宇[1] 王朝兴[1] 李爽 孙诗晴 周子筠 张宇[1] LIU Jia-lei;WANG Yu-liang;ZHAO Hong;SHEN Yu;WANG Chao-xing;LI Shuang;SUN Shi-qing;ZHOU Zi-jun;ZHANG Yu(Key Laboratory of New Drug Discovery and Efficacy Toxicology Evaluation,Institute of Pharmacy,Jiamusi University,Jiamusi 154000,China)

机构地区：[1]佳木斯大学药学院,黑龙江省新药创制与药效毒理学评价重点实验室,黑龙江佳木斯154000

出　　处：《中国实验方剂学杂志》2022年第5期62-70,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：中央支持地方高校改革发展基金项目(2019zyzcdf-01);黑龙江省北药与功能食品特色学科建设项目(2018-TSXK-02);佳木斯大学优秀学科团队项目(JDXKTD-2019005);黑龙江省教育厅基本科研业务费基础研究项目(2017-KYYWF-0590)。

摘　　要：目的:探究百合多糖(LLP)与黄芪多糖(APS)联合发挥抗抑郁作用的机制。方法:60只KM小鼠随机分为空白组,模型组,盐酸氟西汀(8 mg·kg^(-1))组,LLP(0.2 g·kg^(-1))组,APS(0.2 g·kg^(-1))组和多糖联用(LLP+APS,0.1 g·kg^(-1)+0.1 g·kg^(-1))组,每组10只。除空白组外,其余各组均给予慢性不可预知温和应激(CUMS)诱导小鼠抑郁模型,造模第29天,盐酸氟西汀组按相应剂量灌服盐酸氟西汀,各多糖组小鼠灌服相应药物。以小鼠体质量变化、旷场实验、糖水偏爱实验等行为学指标评价小鼠抑郁行为;尼式染色法观察海马CA1区神经元形态变化;酶联免疫吸附测定法(ELISA)检测脑组织及血浆中5-羟色胺(5-HT),促肾上腺皮质激素(ACTH),皮质酮(CORT)的含量变化;蛋白免疫印迹法(Western blot)检测腺苷酸环化酶/环磷酸腺苷/蛋白激酶A(AC/cAMP/PKA)信号通路相关蛋白的表达水平。结果:与空白组比较,模型组小鼠体质量增长缓慢,运动总距离、中心运动距离及糖水偏爱率显著降低(P<0.01),抑郁行为显著,且海马神经元细胞受损严重,5-HT含量显著降低(P<0.01),ACTH和CORT含量显著升高(P<0.01),腺苷酸环化酶6(ADCY6),PKA,cAMP反应元件结合蛋白-1(CREB-1)及脑源性神经营养因子(BDNF)蛋白表达水平显著下降(P<0.01);与模型组比较,LLP组,ASP组和LLP+APS组小鼠抑郁行为均有显著改善(P<0.01),其中LLP+APS抗抑郁作用优于单一多糖,各给药组均能不同程度的缓解海马神经元细胞损伤,显著增加脑组织内5-HT含量(P<0.01),明显降低血浆中ACTH和CORT水平(P<0.05),大幅度上调ADCY6,PKA,CREB-1,BDNF蛋白水平(P<0.05)。结论:LLP和APS联用后抗抑郁效果显著增强,具有良好的正协同性,其作用机制可能与影响神经递质含量、抑制下丘脑-垂体-肾上腺轴(HPA轴)活性、激活AC/cAMP/PKA信号转导通路密切相关。Objective:To explore the mechanism of antidepressant effect of lily polysaccharide (LLP) and astragalus polysaccharide(APS). Method: Sixty KM mice were randomly divided into blank group,model group,fluoxetine hydrochloride(8 mg·kg^(-1))group,LLP(0.2 g·kg^(-1))group,APS(0.2 g·kg^(-1))group and polysaccharide combination(LLP+APS,0.1 g·kg^(-1)+0.1 g·kg^(-1))group,with 10 mice in each group. Except the blank group,the other groups were given chronic unpredictable mild stress(CUMS)induced mouse depression model. On the 29 thday of modeling,fluoxetine hydrochloride group was given corresponding dose of fluoxetine hydrochloride,and polysaccharide groups were given corresponding drug. The depressive behavior of mice was evaluated by behavioral indexes such as body mass change,open field test. The morphological changes of hippocampal CA1 neurons were observed by Nissl staining. The contents of 5-hydroxytryptamine(5-HT),adrenocorticotropic hormone(ACTH),and corticosterone(CORT),in brain tissue and plasma were measured by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression levels of related proteins in adenylate cyclase/cyclic adenylate phosphate/protein kinase A(AC/cAMP/PKA) signal pathway. Result: Compared with the blank group,mice in the model group gained weight slowly,the total distance,central distance and sugar water preference rate decreased significantly(P<0.01),the depressive behavior was significant,the hippocampal neurons were seriously damaged,the content of 5-HT decreased(P<0.01),the contents of ACTH and CORT increased significantly(P<0.01),adenylate cyclase 6(ADCY6),PKA and cAMP response element binding protein-1(CREB-1)and brain-derived neurotrophic factor(BDNF)protein expression decreased significantly(P<0.01). Compared with the model group,depressive behavior of mice in LLP group,APS group and LLP+APS group was significantly improved(P<0.01). The antidepressant effect of LLP+APS was better than that of LLP and APS. Each administration group could alleviate the dama

关 键 词：百合多糖 黄芪多糖 慢性不可预知温和应激 抑郁症 环磷酸腺苷(cAMP)信号转导通路 

分 类 号：R2-0[医药卫生—中医学] R285