对药酸枣仁-合欢花对抑郁模型大鼠海马CA3区细胞凋亡及caspase-12表达的影响
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摘要
目的:研究对药酸枣仁(SZS)-合欢花(AJF)对抑郁模型大鼠海马CA3区细胞凋亡及半胱氨酸天冬氨酸特异性蛋白酶-12(caspase-12)表达的影响,从内质网应激(ERS)角度探讨其抗抑郁作用机制。方法:将雄性SD大鼠按随机数字表法分为正常对照组(Control)、模型组(CUMS)、对药酸枣仁-合欢花组(SZS+AJF)、盐酸文拉法辛组(Venlafaxine),采用孤养加慢性不可预见性温和应激(CUMS)建立抑郁症大鼠模型,并用旷场实验评价各组大鼠行为学改变。应用DNA原位末端缺口标记(TUNEL)法检测海马CA3区神经元凋亡情况,应用免疫组化检测海马CA3区caspase-12表达。结果:与Control组比较,CUMS组大鼠旷场实验得分降低,海马CA3区细胞凋亡率及caspase-12表达显著增加。与CUMS组比较,SZS+AJF组、Venlafaxine组大鼠旷场实验得分显著增加,海马CA3区细胞凋亡率及caspase-12表达显著减少。结论:对药酸枣仁-合欢花能显著改善抑郁模型大鼠的抑郁症状,降低海马CA3区caspase-12表达,抑制海马CA3区细胞凋亡。
Objective: To study the effect of herbal pair of Semen Ziziphi Spinosae( SZS) and Albizia Julibrissin Flower( AJF) on the apoptosis and the expression of cysteinyl aspartate specific proteinase-12( caspase-12) in the hippocampal CA3 region of the depression model rats,and to explore the antidepressant mechanism from the endoplasmic reticulum stress( ERS). Methods: The male SD rats were divided into Control group,CUMS group,SZS + AJF group and Venlafaxine group by random number table. The model of depressive rats was established by using isolated and chronic mild unpredictable stress( CUMS),and the behavior changes in each group were evaluated by open field experiment,and detection of apoptosis in hippocampal CA3 region by TUNEL,and the expression of caspase-12 in the hippocampus CA3 region was detected by immunohistochemistry. Results: Compared with the Control group,the score of the open field experiment in the CUMS group was reduced,the cell structure of the hippocampal CA3 region was destroyed obviously. The rate of apoptosis and the expression of caspase-12 increased significantly( P < 0. 05 or P < 0. 01). Compared with the CUMS group,the score of open field experiment in the rats of SZS + AJF group and Venlafaxine group was significantly increased( P < 0. 05 or P < 0. 01). The rate of apoptosis cells and the expression of caspase-12 decreased significantly( P < 0. 05 or P < 0. 01). Conclusion: The herbal pair of SZS and AJF cansignificantly improve the depressive symptoms of depressive model rats,reduce the expression of caspase-12 in hippocampal CA3 region,and inhibit the apoptosis of CA3 region.
Objective: To study the effect of herbal pair of Semen Ziziphi Spinosae( SZS) and Albizia Julibrissin Flower( AJF) on the apoptosis and the expression of cysteinyl aspartate specific proteinase-12( caspase-12) in the hippocampal CA3 region of the depression model rats,and to explore the antidepressant mechanism from the endoplasmic reticulum stress( ERS). Methods: The male SD rats were divided into Control group,CUMS group,SZS + AJF group and Venlafaxine group by random number table. The model of depressive rats was established by using isolated and chronic mild unpredictable stress( CUMS),and the behavior changes in each group were evaluated by open field experiment,and detection of apoptosis in hippocampal CA3 region by TUNEL,and the expression of caspase-12 in the hippocampus CA3 region was detected by immunohistochemistry. Results: Compared with the Control group,the score of the open field experiment in the CUMS group was reduced,the cell structure of the hippocampal CA3 region was destroyed obviously. The rate of apoptosis and the expression of caspase-12 increased significantly( P < 0. 05 or P < 0. 01). Compared with the CUMS group,the score of open field experiment in the rats of SZS + AJF group and Venlafaxine group was significantly increased( P < 0. 05 or P < 0. 01). The rate of apoptosis cells and the expression of caspase-12 decreased significantly( P < 0. 05 or P < 0. 01). Conclusion: The herbal pair of SZS and AJF cansignificantly improve the depressive symptoms of depressive model rats,reduce the expression of caspase-12 in hippocampal CA3 region,and inhibit the apoptosis of CA3 region.
引文
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[19]施学丽,杜正彩,夏猛,等.合欢花总黄酮对抑郁模型大鼠海马CA3区BDNF和TrkB表达的影响[J].中国实验方剂学杂志,2013,19(18):198-201.DOI:10.11653/syfj2013180198.
[20]施学丽,杜晓娜,郭超峰,等.不同剂量对药酸枣仁-合欢花对抑郁模型大鼠体重及行为学指标的影响[J].广西医学,2018,40(22):2702-2705.DOI:10.11675/j.issn.0253-4304.2018.22.20.
[21]Cao Y,Hao Y,Li H,et al.Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by hightglucose[J].Int J Mol Med,2014,33(4):809-816.DOI:10.3892/ijmm.2014.1642.
[2]施学丽,郭超峰,范丽丽,等.对药酸枣仁-合欢花对老年抑郁症患者生活质量的影响[J].世界科学技术-中医药现代化,2013,15(09):1933-1936.DOI:10.11842/wst.2013.09.013.
[3]樊蔚虹,姚建平,杨清,等.柴胡疏肝散干预卒中后抑郁模型大鼠海马神经细胞凋亡的机制研究[J].中国实验方剂学杂志,2011,17(22):216.DOI:10.13422/j.cnki.syfjx.2011.22.073.
[4]吴薇,刘朝奇.钙网蛋白通过内质网应激介导细胞凋亡的分子机制[J].生物技术通报,2013,(10):24-27.DOI:10.13560/j.cnki.biotech.bull.1985.2013.10.017.
[5]陈娜子,姜潮,李校堃.内质网应激与疾病[J].中国生物工程杂志,2016,36(01):76-85.DOI:10.13523/j.cb.20160111.
[6]Ariyasu D,Yoshida H,Hasegawa Y.Endoplasmic reticulum(ER)stress and endocrine disorders[J].Int J Mol Sci,2017,18(2):382-382.DOI:10.3390/ijms18020382.
[7]Kim EJ,Lee YJ,Kang S,et al.Ionizing radiation activates PERK/e IF2α/ATF4 signaling via ER stress-independent pathway in human vascular endothelial cells[J].Int J Radiat Biol,2014,90(4):306-312.DOI:10.3109/09553002.2014.886793.
[8]Liu Y,Yang N,Hao W,et al.Dynamic proteomic analysis of protein expression profiles in whole brain of Balb/C’mice subjected to unpredictable chronic mild stress:implications for depressive disorders and future therapies[J].Neurochem Int,2011,58(8):904-913.DOI:10.1016/j.neuint.2011.02.019.
[9]Nakagawa T,Zhu H,Morishima N,et al.caspase-12 mediates ER-specific apoptosis and cytotoxicity by amyloid-beta[J].Nature,2000,403(6765):98-103.DOI:10.1038/47513.
[10]施学丽,夏猛,冯秋瑜,等.对药酸枣仁-合欢花对抑郁患者生活质量及神经-内分泌-免疫网络的影响[J].时珍国医国药,2016,27(10):2348-2350.DOI:10.3969/j.issn.1008-0805.2016.10.014.
[11]施学丽,郭超峰,蒋春雷,等.对药酸枣仁-合欢花对抑郁患者认知功能及血清BDNF水平的影响[J].世界科学技术-中医药现代化,2013,15(07):1604-1607.DOI:10.11842/wst.2013.07.021.
[12]贾宝辉,李志刚,卢峻,等.电针抗抑郁研究的模型探讨[J].针刺研究,2005,30(1):22.DOI:10.13702/j.1000-0607.2005.01.005.
[13]郭晓云,江开达.慢性轻度应激抑郁症动物模型研究进展[J].国际精神病学杂志,2007,34(04):216-217.DOI:10.13479/j.cnki.jip.2007.04.002.
[14]施学丽.“心肝同治”治疗抑郁症的理论探讨[J].辽宁中医杂志,2017,44(01):63-65.DOI:10.13192/j.issn.1000-1719.2017.01.020.
[15]党海霞,刘新民.抗抑郁中药研究进展[J].中国现代中药,2008,10(04):35-39.DOI:10.13313/j.issn.1673-4890.2008.04.013.
[16]赵启铎,舒乐新,王颖,等.酸枣仁油对行为绝望小鼠模型的影响[J].中国实验方剂学杂志,2011,17(18):190-192.DOI:10.13422/j.cnki.syfjx.2011.18.020.
[17]宋伟,唐生安,曹冰雁,等.酸枣仁黄酮部位不同配伍的解郁安神作用及谱-效相关性分析[J].中草药,2018,49(05):1123-1131.DOI:10.7501/j.issn.0253-2670.2018.05.021.
[18]刘家荟,郭伟英.合欢花镇静催眠作用的谱效关系研究[J].中药材,2016,39(07):1582-1585.DOI:10.7501/j.issn.0253-2670.2018.05.021.
[19]施学丽,杜正彩,夏猛,等.合欢花总黄酮对抑郁模型大鼠海马CA3区BDNF和TrkB表达的影响[J].中国实验方剂学杂志,2013,19(18):198-201.DOI:10.11653/syfj2013180198.
[20]施学丽,杜晓娜,郭超峰,等.不同剂量对药酸枣仁-合欢花对抑郁模型大鼠体重及行为学指标的影响[J].广西医学,2018,40(22):2702-2705.DOI:10.11675/j.issn.0253-4304.2018.22.20.
[21]Cao Y,Hao Y,Li H,et al.Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by hightglucose[J].Int J Mol Med,2014,33(4):809-816.DOI:10.3892/ijmm.2014.1642.
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