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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 explore the mechanism of antidepressant GBE50 by observing the behavior of GBE50 and the NLRP3 inflammasome in depression model rats. Methods: Chronic unpredictable stress depression model (CUMS) was used. Forty male SD rats were randomly divided into 4 groups (control group, model group, fluoxetine group, GBE50 group). After 3 weeks of stress stimulation, the use of sugar preference experiment, forced swimming experiment evaluation model, and remove the model unsuccessful mice. The rats in the control group and the model group were intragastrically given 1% CMC, fluoxetine (10mg / kg) was given to the fluoxetine group, and GBE50 (100mg / kg) was given to the rats in GBE50 group for 3 weeks. Sugar preference test, forced swimming test, Western blot was used to detect the content of NLRP3 inflammasome and its related activation signal pathway proteins in hippocampus of rats in each group. Results: The results of sweet water preference test showed that compared with the model group, GBE50 (100 mg / kg) could significantly increase the sugar consumption of depressed rats. Forced swimming test results show that, compared with the model group, GBE50 (100mg / kg) can significantly increase the forced swimming of depressed rats struggling time. Western blot showed that CUMS significantly increased the protein expression of NLRP3, ASC, Caspase-1, IL-1β, TLR4, P2X7, P-IKKα / β and P-NF-κB in the model group The expressions of NLRP3, ASC, Caspase-1, IL-1β, TLR4, P2X7, P-IKKα / β and P-NF-κB were significantly decreased. CONCLUSION: GBE50 (100 mg / kg) can improve CUMS-induced depression-like behavior in rats, and its mechanism may be related to the regulation of TLR4 / NF-κB signaling pathway and the inhibition of NLRP3 inflammasome activation.