【摘要】 目的研究原花青素(PCA)对溃疡性结肠炎(UC)小鼠抑郁样症状的作用及相关机制。方法 24只清洁级雄性小鼠随机分为对照(NS)组、模型(UC)组和PCA组,UC组和PCA组给予5%右旋葡聚糖硫酸钠(DSS)自由饮用水7 d,而NS组给予正常饮用水对照,造模的同时,PCA组给予75 mg/kg PCA灌胃,1次/d,连续7 d,其他各组给予等体积生理盐水代替,并记录疾病活动指数(DAI)评分。在最后一次灌胃后对各组小鼠进行行为学考察,处死动物取大脑海马组织,Western印迹测定海马组织白细胞介素(IL)-6、核因子(NF)-κB蛋白表达量。尼氏染色观察小鼠海马神经元损伤变化。结果与NS组相比,UC组悬尾和强迫游泳的不动时间明显减少(P<0.05),海马组织中IL-6、NF-κB蛋白表达量显著增多(P<0.05),海马CA3区神经元损伤明显;PCA组与UC组比较,可明显提高小鼠悬尾和强迫游泳的不动时间(P<0.05),增加海马组织中IL-6、NF-κB蛋白表达量(P<0.05),减少海马神经元损伤。结论 PCA对UC小鼠的抑郁样行为具有保护作用,这种保护作用可能与抑制小鼠大脑海马组织中NF-κB的活化,降低IL-6等炎性细胞因子的表达,从而改善海马神经元损伤有关。更多还原

【Abstract】 Objective To explore the effect and mechanism of proanthocyanidin(PCA) in treatment of depressive behaviors in a mouse model of ulcerative colitis(UC) and identify the underlying mechanism.Methods 24 ICR male mice were divided into NS, UC and PCA groups. The UC model was induced by dextran sulfate sodium DSS for 7 days. Meanwhile, the PCA group was given PCA 75 mg/kg once a day for 7 days by gavage, and the other groups were given an equal volume of normal saline. The disease activity index(DAI) was used to measure the changes induced by DSS. Forced swimming and tail suspension tests were used to assess depressive behaviors. Neuronal survival and hippocampal expression of IL-6 and nuclear factor(NF)-κB were also detected.Results Compared with the NS group, the immobility time of forced swimming and tail suspension tests were significantly reduced(P<0.05), the expressions of IL-6 and NF-κB protein in the hippocampal tissue were significantly increased(P<0.05), and the neuronal cell injury in the CA3 region of the hippocampus was significantly decreased in the UC group(P<0.05). Compared with the UC group, PCA group significantly increased the immobility time of tail suspension and forced swimming(P<0.05), increased the expressions of IL-6 and NF-κB protein in the hippocampus(P<0.05), and reduced the neuronal cell injury.Conclusions Proanthocyanidins could play an anti-depression function induced by UC. The protective effect might be related to inhibiting the activation of NF-κB in the hippocampal tissue and reducing the expression of inflammatory cytokines such as IL-6, thus improving hippocampal neuron injury.更多还原