[1]李 玥,陈俊逾.姜黄醇对大鼠抑郁的改善作用及机制实验研究[J].陕西医学杂志,2024,(3):303-307.[doi:DOI:10.3969/j.issn.1000-7377.2024.03.003]
　LI Yue,CHEN Junyu.Improving effect and mechanism of curcumol on depressed rats[J].,2024,(3):303-307.[doi:DOI:10.3969/j.issn.1000-7377.2024.03.003]
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姜黄醇对大鼠抑郁的改善作用及机制实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年3期
页码:
303-307
栏目:
基础研究
出版日期:
2024-03-05

文章信息/Info

Title:
Improving effect and mechanism of curcumol on depressed rats
作者:
李 玥; 陈俊逾
(新疆医科大学第四临床医学院神志科,新疆 乌鲁木齐 830099)
Author(s):
LI Yue; CHEN Junyu
(Department of Mental Health,the Fourth Clinical Medical College of Xinjiang Medical University,Urumqi 830099,China)
关键词:
抑郁;  姜黄醇;  核受体共激活因子4;  铁自噬;  铁死亡;  大鼠
Keywords:
Depression;  Curcumol;  Nuclear receptor coactivator 4;  Iron autophagy;  Ferroptosis;  Rat
分类号:
R 285
DOI:
DOI:10.3969/j.issn.1000-7377.2024.03.003
文献标志码:
A
摘要:
目的:探讨姜黄醇对大鼠抑郁的改善作用及机制。方法:将18只大鼠作为假手术组,其余大鼠(72只)通过铁死亡诱导剂Erastin诱导抑郁症模型。将造模成功的抑郁大鼠随机分为Erastin组、姜黄醇组(10 mg/kg姜黄醇)、姜黄醇+pcDNA-NC组(10 mg/kg姜黄醇+尾静脉注射pcDNA-NC)、姜黄醇+pcDNA-核受体共激活因子4(NCOA4)组(10 mg/kg姜黄醇+尾静脉注射pcDNA-NCOA4),每组18只。假手术组和Erastin组给予等量0.9%氯化钠溶液。采用糖水偏好实验(SPT)、旷场实验(OFT)、悬尾实验(TST)、强迫游泳实验(FST)进行动物行为学评价。采用透射电子显微镜观察海马组织线粒体形态。采用ELISA试剂盒测定铁含量。采用Western blot检测海马组织自噬及铁死亡相关蛋白表达。结果:假手术组海马组织线粒体结构正常。与假手术组比较,Erastin组神经元中线粒体肿胀,线粒体嵴丢失,蔗糖水偏好、OFT中心区移动距离、OFT交叉次数、谷胱甘肽过氧化物酶4(GPX4)蛋白表达水平显著降低,FST静止时间、TST静止时间、OFT静止时间、总铁和亚铁含量以及NCOA4、微管相关蛋白轻链3-Ⅱ(LC3-Ⅱ)/ LC3-Ⅰ、环氧合酶2(COX2)、长链脂酰辅酶A合成酶4(ACSL4)、环加氧酶2(PTGS2)蛋白表达水平显著升高(均P<0.05)。与Erastin组比较,姜黄醇组线粒体肿胀、线粒体嵴丢失现象改善,蔗糖水偏好、OFT中心区移动距离、OFT交叉次数、GPX4蛋白表达水平显著升高,FST静止时间、TST静止时间、OFT静止时间、总铁和亚铁含量以及NCOA4、LC3-Ⅱ/LC3-Ⅰ、COX2、ACSL4、PTGS2蛋白表达水平显著降低(均P<0.05)。姜黄醇+pcDNA-NCOA4组与Erastin组海马组织线粒体损伤现象相似。与姜黄醇组、姜黄醇+pcDNA-NC组比较,姜黄醇+pcDNA-NCOA4组蔗糖水偏好、OFT中心区移动距离、OFT交叉次数、GPX4蛋白表达水平显著降低,FST静止时间、TST静止时间、OFT静止时间、总铁和亚铁含量以及NCOA4、LC3-Ⅱ/LC3-Ⅰ、COX2、ACSL4、PTGS2蛋白表达水平显著升高(均P<0.05)。结论:姜黄醇可能通过下调NCOA4介导的铁自噬调控铁死亡,进而起到抗抑郁作用。
Abstract:
Objective:To explore the improving effect and mechanism of curcumol on depressed rats.Methods:Eighteen rats were selected as the sham surgery group and the rest of the rats(72 rats)were induced into the depression model by Erastin.The successful depression rats were randomly grouped into the Erastin group,the curcumol group(10 mg/kg curcumol),the curcumol+pcDNA-NC group(10 mg/kg curcumol+pcDNA-NC via tail vein),and the curcumol+pcDNA-nuclear receptor coactivator 4(NCOA4)group(10 mg/kg curcumol+pcDNA-NCOA4 via tail vein),with 18 rats in each group.The sham surgery group and the Erastin group were given 0.9% sodium chloride solution.They were applied to ethology evaluation through sugar preference test(SPT),open field test(OFT),tail suspension test(TST)and forced swimming test(FST).Transmission electron microscopy was applied to observe the morphology of mitochondria.The iron content was determined by ELISA kit.Western blot was applied to detect the expression of autophagy protein and ferroptosis protein in hippocampus.Results:The mitochondrial structure of hippocampus in the sham surgery group was normal.Compared with the sham surgery group,the mitochondria in the neurons of the Erastin group were swollen,the crista was lost,the sucrose water preference,the distance of central area movement,the number of crossings,and the level of glutathione peroxidase 4(GPX4)protein were obviously reduced,the FST resting time,TST resting time,OFT resting time,total iron content,ferrous content,the levels of NCOA4,microtubule-associated protein light chain 3-Ⅱ(LC3-Ⅱ)/LC3-Ⅰ,cyclooxygenase 2(COX2),long-chain acyl coenzyme A synthase 4(ACSL4)and cyclooxygenase 2(PTGS2)proteins were obviously increased(all P<0.05).Compared with the Erastin group,the mitochondrial swelling and crista loss in the curcumol group were improved,the sucrose water preference,the distance of central area movement,the number of crossings,and the level of GPX4 protein were obviously increased,the FST rest time,TST rest time,OFT rest time,total iron content,ferrous content,the levels of NCOA4,LC3-Ⅱ/LC3-Ⅰ,COX2,ACSL4 and PTGS2 proteins were obviously reduced(all P<0.05).The damage of hippocampal mitochondria in curcumol+pcDNA-NCOA4 group was similar to that in Erastin group.Compared with curcumol group and curcumol+pcDNA-NC group,the sucrose water preference,the distance of central area movement,the number of crossings,and the level of GPX4 protein were obviously reduced,the FST resting time,TST resting time,OFT resting time,total iron content,ferrous content,the levels of NCOA4,LC3-Ⅱ/LC3-Ⅰ,COX2,ACSL4 and PTGS2 proteins were obviously increased(all P<0.05).Conclusion:Curcumin may regulate iron death by down-regulating NCOA4-mediated iron autophagy,and play an antidepressant role.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(82260915)
更新日期/Last Update: 2024-03-05