银杏酮酯(GBE50)抑制NLRP3炎症小体活性改善大鼠抑郁样行为  被引量:15

Ginkgo biloba extract 50(GBE50) improved depressive behavior in rats by suppressing the activation of NLRP3 inflammasome

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作  者:刘富群[1] 高崎 王丹丹 朱国琴 张志雄[1] 

机构地区:[1]上海中医药大学生理学教研室,上海201203 [2]上海上药杏灵科技药业股份有限公司,上海210703

出  处:《中药药理与临床》2017年第5期54-58,共5页Pharmacology and Clinics of Chinese Materia Medica

基  金:上海市科委计划项目(13DZ1970200)

摘  要:目的:本实验通过观察银杏酮酯(GBE50)对抑郁模型大鼠行为学及NLRP3炎症小体作用,探索GBE50抗抑郁的机制。方法:采用慢性不可预见性应激抑郁模型(CUMS)。将40只雄性SD大鼠随机分为4组(对照组、模型组、氟西汀组、GBE50组)。经3周应激刺激后,运用糖水偏爱实验、强迫游泳实验评价造模,并剔除造模不成功老鼠。然后对照组、模型组给予1%CMC灌胃,氟西汀组给予氟西汀(10mg/kg)灌胃,GBE50组给予GBE50(100mg/kg)灌胃,持续3周,最后对各实验组进行糖水偏爱实验、强迫游泳实验测试,并运用Western检测各组大鼠海马组织NLRP3炎症小体及其相关激活信号通路蛋白的表达含量。结果:糖水偏爱实验结果显示,与模型组相比,GBE50(100mg/kg)可以明显增加抑郁大鼠的糖水消耗量。强迫游泳实验结果显示,与模型组相比,GBE50(100mg/kg)可以明显增加抑郁大鼠强迫游泳的挣扎时间。Western结果显示:CUMS可以明显增加模型组NLRP3、ASC、Caspase-1、IL-1β、TLR4、P2X7、P-IKKα/β、P-NF-κB的蛋白表达,而GBE50(100mg/kg)治疗后NLRP3、ASC、Caspase-1、IL-1β、TLR4、P2X7、P-IKKα/β、P-NF-κB蛋白表达明显减少。结论:GBE50(100mg/kg)可以改善CUMS诱导的大鼠的抑郁样行为,而其作用机制与调控TLR4/NF-κB信号通路,抑制NLRP3炎症小体激活有关。Objective: To investigate the effect of Ginkgo biloba extract 50(GBE50) on behavior and NLRP3 inflammasome in depressive rats,confirme its mechanisms on depression. Methods: Models were established by chronic unpredictable mild stress. Forty male SD rats were randomly divided into four groups(the control group,the model group,Fluoxetine group and GBE50 group). The sucrose preference test and forced swim test were applied to evaluate depressive rats after 3 weeks stress and unqualified rats were removed. Then 1% CMC was administered by gavage in the control group and the model group,Fluoxetine(10 mg/kg) was administered by gavage in fluoxetine group,GBE50(100 mg/kg)suspended in 1% CMC was administered by gavage in GBE50 group,once daily for next 3 weeks. At last,the sucrose preference test and forced swim test were performed,the protein level of NLRP3 inflammasome and its activation of signaling pathways in hippocampal were detected by Western blot. Results: Sucrose preference test showed that the sucrose intake in GBE50 group(100 mg/kg) was more than that in the model group. Forced swim test showed that the climbing time in GBE50 group(100 mg/kg) displayed a remarkable increase than that in the model group. Western blot assay showed that protein levels of NLRP3,ASC,Caspase-1,IL-1β,TLR4,P2 X7,P-IKKα/β,P-NF-κB were obviously increased after Chronic Unpredictable Mild Stress,but GBE50(100 mg/kg) decreased these protein levels,the decline was significant compared with the model group(P〈0. 01). Conclusion: GBE50(100 mg/kg) could alleviate depressive symptoms in CUMS model rats,it is related with controlling the TLR4/NF-κB signals and suppressing the activation of NLRP3 inflammasome.

关 键 词:银杏酮酯 抑郁症 NLRP3炎症小体 

分 类 号:R285.5[医药卫生—中药学]

 

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