蒺藜皂苷抗抑郁作用及机制研究  

Antidepressant effect and mechanism of Gross saponins of Tribulus terrestris

作　　者：张伟[1] 俞仲毅[2] 梅泰中 胡凯莉[3] 刘梅[1] 

机构地区：[1]上海中医药大学上海中医健康服务协同创新中心,上海201203 [2]上海中医药大学科技实验中心,上海201203 [3]上海中医药大学穆拉德中药现代化研究中心,上海201203

出　　处：《中国药理学通报》2017年第3期343-348,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年基金资助项目(No 81202924);上海中医药大学预算内项目(No 2015YSN29)

摘　　要：目的探讨蒺藜皂苷的抗抑郁作用及机制。方法采用孤立大鼠加慢性轻度不可预见性应激方法造抑郁大鼠模型,进行开放旷场,悬尾行为学测试,用LC-MS/MS液质联用法检测大鼠血液中5-羟色胺(5-HT)、γ氨基丁酸(GABA)、去甲肾上腺素(NE)、谷氨酸(Glu)含量变化。实时定量PCR检测海马吲哚胺2,3-双加氧酶(IDO)、核转录因子-κB(NF-κB)、炎性细胞因子白介素1β(IL-1β)基因表达。Western blot检测海马中吲哚胺2,3-双加氧酶(IDO)、细胞因子NF-κB(p65)蛋白水平表达。结果与空白组比较,模型组小鼠旷场运动距离、站立次数和悬尾不动时间明显增加(P<0.05),血液中5-羟色胺明显下降(P<0.05),海马中IDO、NF-κB、IL-1β基因表达上调,IDO、NF-κB蛋白水平明显上调(P<0.05)。与模型组比较,蒺藜皂苷给药组能明显减少慢性应激导致大鼠旷场运动距离、站立次数和悬尾不动时间(P<0.05)。蒺藜皂苷给药组能明显提高大鼠血液中5-羟色胺含量(P<0.05),上调海马中抗炎因子IL-10基因表达,明显下调IDO、IL-1β基因表达(P<0.05),明显下调IDO蛋白表达水平(P<0.05)。结论蒺藜皂苷能明显改善动物行为学,具有抗抑郁作用,其作用可能与提高血液中5-羟色胺水平,下调色氨酸前体代谢酶吲哚胺2,3-双加氧酶(IDO)、IL-1β基因表达和降低吲哚胺2,3-双加氧酶(IDO)蛋白表达水平有关。Aim Tostudytheantidepressanteffectand mechanism of Gross saponins of Tribulus terrestris. Methods Themodelofdepressionwasestablishedby unpredictable chronic mild stress（UCMS）,then open filed test （OFT）and tail suspension test （TST）were used to evaluate the behavioral changes.LC-MS/MS method was employed to measure blood neurotransmit-ters.mRNA expressions of IDO,IL-10 and IL-1βwere detected by quantitative PCR method.Hippocampus protein expression was detected by Western blot.Re-sults Comparedwithcontrolgroup,modelgroup＇s total distance,number of standing and tail suspension fixed time increased significantly （P 〈0. 05 ）,Neuro-transmitter level of 5-HT in the blood was significantly decreased（P〈0. 05 ）.mRNA expression of IDO and IL-1βwas increased in hippocampus.Protein expres-sion of IDO was significantly increased in hippocampus （P 〈0. 05 ）.Compared with model group,the treat-ment group was significantly decreased in total distance,number of standing and tail suspension fixedtime（P〈0. 05）.Neurotransmitter level of 5-HT in the blood and mRNA expression of IL-10 in hippocampus were significantly increased after treatment （P 〈0. 05 ）.mRNA and protein expression of IDO were ob-viously down-regulated in hippocampus （P 〈0. 05 ）. Conclusions GrosssaponinsofTribulusterrestriscan obviously improve rat behavior and show antidepressanteffect,which can increase neurotransmitter level of 5-HT in the blood,down-regulate mRNA expression of IDO and IL-1β,and obviously increase protein expres-sion levels of IDO in hippocampus（P〈0. 05 ）.

关 键 词：蒺藜皂苷 抑郁 神经递质 慢性轻度不可预见性刺激 5-羟色胺 吲哚胺2 3-双加氧酶 

分 类 号：R-332[医药卫生] R284.1