β-细辛醚对抑郁模型大鼠海马组织内质网应激调控因子GRP78,ATF6,XBP1表达的影响

发布时间：2018-11-12 08:49

【摘要】：目的:研究石菖蒲有效成分β-细辛醚对慢性不可预见性温和刺激(chronic unpredictable mild stress,CUMS)大鼠抑郁模型内质网应激相关因子的影响。方法:100只大鼠随机分为5组:正常对照组、模型组、氟西汀组、β-细辛醚低剂量组和高剂量组。建立CUMS模型,建模d 8开始,qd,灌胃(ig)给予氟西汀(10mg·kg~(-1))、β-细辛醚(25和50 mg·kg~(-1))。分别于实验的d 0和d 29进行旷场实验(open field test)和糖水偏爱度实验(SPT)。流式细胞术检测各组大鼠海马组织细胞凋亡情况;Western Blot技术检测各组大鼠海马组织GRP78,ATF6,XBP1蛋白表达。结果:各组大鼠在造模实验前水平运动和垂直运动得分及糖水偏爱度均无显著差异(P0.05);28 d慢性不可预见性温和刺激后,与对照组相比,CUMS大鼠水平运动、垂直运动得分及糖水偏爱度均显著减少(P0.05);β-细辛醚组和氟西汀组相比模型组指标明显升高(P0.05)。经流式细胞术检测,CUMS大鼠的海马细胞凋亡率明显增加(P0.05);β-细辛醚组和氟西汀组细胞凋亡率明显下降(P0.05)。经Western Blot检测,CUMS大鼠ATF6蛋白表达显著上调(P0.05),GRP78和XBP1蛋白表达无明显改变(P0.05);β-细辛醚组和氟西汀组显著抑制ATF6蛋白表达下降(P0.05),并升高GRP78和XBP1蛋白表达(P0.05)。结论:β-细辛醚可明显改善CUMS大鼠抑郁样行、减轻内质网应激状态并减少大鼠海马组织神经元细胞凋亡发生。
[Abstract]:Aim: to study the effect of 尾-asarone on endoplasmic reticulum stress related factors in chronic unpredictable mild stimulation of (chronic unpredictable mild stress,CUMS in rats with depression. Methods: 100 rats were randomly divided into 5 groups: normal control group, model group, fluoxetine group, low-dose 尾 -asarone group and high-dose group. The CUMS model was established and the model was established on d 8. Qd, was given (ig) intragastrically with 10mg kg~ (-1), 尾 -Asarone) (25 and 50 mg kg~ (-1). Open field experiment (open field test) and sugar water preference test (SPT). Were carried out on d 0 and d 29, respectively. Apoptosis of hippocampal tissue in each group was detected by flow cytometry.; Western Blot technique was used to detect the expression of GRP78,ATF6,XBP1 protein in hippocampal tissue of rats in each group. Results: there was no significant difference in the scores of horizontal and vertical movements and the degree of preference of sugar water between the three groups (P0.05). After 28 days of chronic unpredictable mild stimulation, compared with the control group, the scores of horizontal exercise, vertical exercise and sugar water preference of CUMS rats were significantly decreased (P0.05). 尾-asarone group and fluoxetine group were significantly higher than the model group (P0.05). Flow cytometry showed that the apoptosis rate of hippocampal cells in CUMS rats was significantly increased (P0.05), and that in 尾 -asarone group and fluoxetine group was significantly decreased (P0.05). The expression of ATF6 protein was significantly up-regulated by Western Blot in CUMS rats (P0.05), but the expression of GRP78 and XBP1 was not changed (P0.05). 尾 -asarone group and fluoxetine group significantly inhibited the expression of ATF6 protein (P0.05), and increased the expression of GRP78 and XBP1 protein (P0.05). Conclusion: 尾 -asarone can significantly improve the depressive behavior of CUMS rats, alleviate the stress state of endoplasmic reticulum and decrease the neuronal apoptosis in hippocampus of rats.
【作者单位】：齐齐哈尔医学院;
【基金】：黑龙江省科技厅攻关项目(PC13S06) 齐齐哈尔市科技局社会发展公关资助项目(SFZD-2014021)
【分类号】：R285.5;R-332

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