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DOI:
:2017,(5):60-65
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银杏酮酯对抑郁症大鼠抑郁样行为及NLRP3炎症小体的作用
刘富群1,高崎2,王丹丹2,朱国琴2,张志雄1
(1.上海中医药大学基础医学院生理学教研室(上海201203) ;2.上海杏灵科技药业股份有限公司(上海210703))
Effects of Ginkgo Biloba Extract on Depression-like Behavior and NLRP3 Inflammasome in Depressive Rats
LIU Fu-qun1, GAO Qi2, WANG Dan-dan2, ZHU Guo-qin2, ZHANG Zhi-xiong1
(1.Department of Physiology,School of Basic Medical Science, Shanghai University of Traditional Chinese Medicine,Shanghai, 201203;2.Shanghai Xingling Sci.& Tech. Pharmaceutical Co.,Ltd.,Shanghai,210703)
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投稿时间:2017-05-10    
中文摘要:   目的:观察银杏酮酯(GBE50)对脂多糖(LPS)诱导的抑郁症模型大鼠行为学及NLRP3炎症小体的作用,探讨GBE50 抗抑郁的作用机制。  方法:将40只雄性SD大鼠随机分为对照组、模型组、GBE50组、氟西汀组,每组10只。除对照组外,均采用LPS腹腔注射诱导大鼠抑郁。GBE50组每天以GBE50(100 mg/kg)灌胃,氟西汀组每天以氟西汀(10 mg/kg)灌胃,其余各组大鼠每天以1%CMC灌胃。4周后进行强迫游泳实验、旷场试验;Western-blot检测各组大鼠海马组织NLRP3、凋亡相关微粒蛋白(ASC)、Caspase-1、白介素-1β(IL-1β)的蛋白表达量;Elisa检测大鼠血清促炎性因子肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平。  结果:模型组大鼠强迫游泳的不动时间、旷场试验中总路程和垂直站立次数较对照组明显下降,GBE50组大鼠的强迫游泳不动时间、旷场试验中总路程和垂直站立次数较模型组明显改善,两组比较差异具有统计学意义(P<0.05)。Western-blot结果显示,与对照组比较,模型组大鼠海马组织NLRP3、ASC、Caspase-1、IL-1β的蛋白表达明显增加(P<0.05);GBE50组NLRP3、ASC、Caspase-1、IL-1β蛋白表达较模型组明显降低,两组比较差异具有统计学意义(P<0.05)。Elisa结果显示,与对照组相比,模型组大鼠血清促炎性因子TNF-α、IL-6分泌明显增加(P<0.05),GBE50组TNF-α、IL-6较模型组明显降低,两组比较差异具有统计学差异(P<0.05)。  结论:GBE50可以抑制抑郁症大鼠的抑郁样行为,其作用机制可能与抑制NLRP3炎症小体活性及促炎性因子分泌有关。
Abstract:  Objective:To observe the effects of ginkgo biloba extract(GBE50)on behavior and Nod-like receptor pyrin domain-containing protein 3(NLRP3)inflammasome in lipopolysaccharide(LPS)-induced depression rats,and discuss the mechanism of GBE50 in the treatment of depression.   Methods: 40 male SD rats were randomly divided into the control group,model group,GBE50 group and fluoxetine group, 10 rats in each group. Except the control group,the other groups were treated with LPS by intraperitoneal injection to induce the rat model of depression. The GBE50 group was treated with GBE50 by intragastric administration at daily dose of 100 mg/kg,the fluoxetine group was treated with fluoxetine by intragastric administration at daily dose of 10 mg/kg,and the rats in the other groups were treated with 1%CMC by intragastric administration. After administration for 4 weeks,the forced swimming test and open field test were performed. The protein expressions of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),cysteinyl aspartate specific proteinase-1(Caspase-1)and interleukin-1β(IL-1β)in hippocampus of rats in each group were detected by Western blot,and the serum levels of proinflammatory cytokines tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by ELISA.   Results: Compared with the control group,the immobility time of rats in forced swimming test and the total distance and vertical standing times in open field test were obviously decreased in the model group;compared with the model group,the immobility time of rats in forced swimming test and the total distance and vertical standing times in open field test were obviously increased in the GBE50 group,with statistical differences(P<0.05).The results of Western blot showed that,compared with the control group,the protein expressions of NLRP3,ASC,Caspase-1 and IL-1β in hippocampus of rats were obviously increased in the model group(P<0.05);compared with the model group,the protein expressions of NLRP3,ASC,Caspase-1 and IL-1β were obviously decreased in the GBE50 group,with statistical differences(P<0.05).The results of ELISA showed that,compared with the control group,the serum levels of TNF-α and IL-6 were obviously increased in the model group(P<0.05);compared with the model group,the serum levels of TNF-α and IL-6 were obviously decreased in the GBE50 group,with statistical differences(P<0.05).   Conclusion: GBE50 can suppress the depression-like behavior in depressive rats,and its mechanism may be associated with the inhibition of NLRP3 inflammasome activity and proinflammatory cytokines secretion.
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基金项目:上海市科委计划项目(13DZ1970200)
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