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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。
OBJECTIVE: To observe the effect of GBE50 on the behavior and NLRP3 inflammasome in rats induced by lipopolysaccharide (LPS), and to explore the mechanism of antidepressant effect of GBE50. Methods: Forty male SD rats were randomly divided into control group, model group, GBE50 group and fluoxetine group, with 10 rats in each group. In addition to the control group, rats were treated with LPS intraperitoneal injection of depression. The GBE50 group was orally gavaged with GBE50 (100 mg / kg) every day. The fluoxetine group was orally administered with fluoxetine (10 mg / kg) daily, while the other groups were orally administered with 1% CMC daily. After 4 weeks, forced swimming test and open-field test were performed. The protein expression of NLRP3, ASC, Caspase-1 and IL-1β in hippocampus were detected by Western- Elisa was used to detect the levels of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Results: The immobility time of forced swimming in model group was significantly lower than that in control group in the open field test. The swimming time of forced swimming in the GBE50 group, the total distance and vertical standing times in the open-field test Compared with the model group significantly improved, the difference between the two groups was statistically significant (P <0.05). Western-blot results showed that compared with the control group, the protein expression of NLRP3, ASC, Caspase-1 and IL-1βin the hippocampus of the model group was significantly increased (P <0.05) 1βprotein expression was significantly lower than the model group, the difference between the two groups was statistically significant (P <0.05). The result of Elisa showed that compared with the control group, the secretion of pro-inflammatory cytokines TNF-α and IL-6 in the model group increased significantly (P <0.05), and the levels of TNF-α and IL-6 in the GBE50 group were significantly lower than those in the model group The difference between the two groups was statistically significant (P <0.05). Conclusion: GBE50 can inhibit depression-like behavior in depression rats, and its mechanism may be related to the inhibition of the activity of NLRP3 inflammasome and the secretion of proinflammatory cytokines.