长春西汀对抑郁大鼠情感障碍相关脑区小胶质细胞活性的影响

Effect of vinpocetine on microglia activity in brain regions related to affective disorders of depression rats

目的观察长春西汀对抑郁大鼠情感障碍相关脑区小胶质细胞(MG)活性的影响,并探讨相关机制。方法40只大鼠随机挑选8只作为对照组,其余建立抑郁模型,并随机分为模型组、低剂量实验组和高剂量实验组,各8只。低、高剂量实验组分别给予长春西汀0.5和1.0 mg·kg^(-1)腹腔注射,对照组及模型组均给予等量生理盐水腹腔注射。每天1次,连续干预7 d。末次干预后次日进行糖水消耗实验;检测海马、杏仁核组织炎症因子含量;以蛋白质印迹(Western blot)法检测脑组织Toll样受体4(TLR4)、核转录因子κB p65(NF-κB p65)和p-NF-κB p65蛋白表达。结果对照组、模型组和低、高剂量实验组的糖水偏嗜度分别为(81.25±9.15)%,(52.68±7.14)%,(63.57±8.49)%和(75.21±9.05)%,海马肿瘤坏死因子-α(TNF-α)含量分别为(2.43±0.68),(8.62±1.52),(5.03±1.08)和(3.95±0.79)pg·mL^(-1),杏仁核TNF-α含量分别为(25.63±4.97),(51.20±6.11),(40.09±5.52)和(32.02±5.23)pg·mL^(-1),脑组织TLR4蛋白表达量分别为0.10±0.02,1.53±0.29,0.74±0.11和0.52±0.06,p-NF-κB p65/NF-κB p65分别为0.30±0.04,0.96±0.12,0.51±0.06和0.42±0.05。模型组的上述指标与对照组比较,低剂量实验组的上述指标与模型组比较,高剂量实验组的上述指标与低剂量实验组比较,差异均有统计学意义(均P<0.05)。结论长春西汀可改善抑郁大鼠抑郁样行为,抑制情感障碍相关脑区炎症反应及小胶质细胞活化,且呈剂量依赖性,可能与抑制TLR4/NF-κB信号通路有关。

Objective To observe the effect of vinpocetine on the activity of microglia(MG)in brain regions related to affective disorders of depression rats,and to explore the related mechanisms.Methods Eight of 40 rats were randomly selected as control group;the rest were established as depression models and were randomly divided into model group,experimental-L group,experimental-H group,each with 8 rats.The experimental-L and experimental-H groups were given intraperitoneal injection of vinpocetine 0.5 and 1.0 mg·kg^(-1)respectively.The control group and model group were injected intraperitoneally with the same amount of normal saline.Once a day,continuous intervention for 7 days.The sugar water consumption test was performed the day after the last intervention.The inflammatory factors in hippocampus and amygdala were detected.Western blot was used to detect Toll-like receptor 4(TLR4),nuclear transcription factorκB p65(NF-κB p65),p-NF-κB p65 protein expression in brain tissue.Results The syrup partiality of control group,model group,experimental-L group and experimental-H group were(81.25±9.15)%,(52.68±7.14)%,(63.57±8.49)%,(75.21±9.05)%,the tumor necrosis factor-α(TNF-α)content in hippocampal were(2.43±0.68),(8.62±1.52),(5.03±1.08),(3.95±0.79)pg·mL^(-1),the tumor necrosis factor-α(TNF-α)content in amygdala were(25.63±4.97),(51.20±6.11),(40.09±5.52),(32.02±5.23)pg·mL^(-1),the expression of TLR4 protein in brain tissue were 0.10±0.02,1.53±0.29,0.74±0.11,0.52±0.06,the p-NF-κB p65/NF-κB p65 were 0.30±0.04,0.96±0.12,0.51±0.06,0.42±0.05.Compared between the model group and the control group,between the experimental-L group and the model group,between the experimental-H group and the experimental-L group,the differences were statistcally significant(all P<0.05).Conclusion Vinpocetine can ameliorate depression-like behavior in depressed rats,inhibit the inflammatory response and MG activation in affective disorder-related brain areas in a dose-dependent manner,which may be related to the inhibition of TLR4/NF-κB signaling pathway.