姜黄素通过抗应激作用改善脑缺血再灌注大鼠工作记忆

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (12): 1321-1325.

• 基础研究 • 下一篇

姜黄素通过抗应激作用改善脑缺血再灌注大鼠工作记忆

姬斌, 刘绪华, 杨芳骅, 周瑞, 曹红, 李军

温州医科大学附属第二医院麻醉科,温州 325027,浙江

收稿日期:2014-06-05 修回日期:2014-11-17 发布日期:2020-07-20
通讯作者: 李军,通信作者,男,博士,教授,研究方向:围术期重要脏器保护。Tel:0577-88002925 E-mail:lijun0068@163.com
作者简介:姬斌,男,硕士,医师,研究方向:围术期脑缺血再灌注损伤的研究。Tel:0577-88002925 E-mail:wzmcjb@163.com
基金资助:
国家自然科学基金(81271204);浙江省自然科学基金(Y2100231)

Curcumin improves the impaired working memory in cerebral ischemia-reperfusion rats by inhibiting the stress response

JI Bin, LIU Xu-hua, YANG Fang-hua, ZHOU Rui, CAO Hong, LI Jun

Department of Anesthesiology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China

Received:2014-06-05 Revised:2014-11-17 Published:2020-07-20

摘要/Abstract

摘要： 目的: 探讨姜黄素预先给药对大鼠全脑缺血再灌注后空间工作记忆改善作用的机制。方法: 成年雄性SD大鼠120只,经T迷宫训练后按随机数字表法分成5组:假手术组(SHAM组)、脑缺血再灌注组(IR组)、姜黄素组(CUR组)、皮质酮组(CORT组)和姜黄素+皮质酮组(CUR+CORT组),每组24只。各组给予相应药物、溶媒注射,1 h 后全脑缺血 10 min 后再灌注,于再灌注 7 d 行T迷宫检测工作记忆,于再灌注 2 h、1、3、7 d 采血清和脑组织标本,TUNEL法检测海马CA1区神经元凋亡情况,ELISA检测血清皮质酮(CORT)和海马脑源性神经营养因子(BDNF)的表达。结果: 与SHAM组比较,IR组CORT水平增加(164±36 vs 92±24,P<0.05),海马BDNF含量降低(8.7±2.8 vs 19.4±5.1,P<0.05),海马CA1区凋亡神经元数目增加(233±22 vs 21±4,P<0.01),T迷宫正确率降低(65%±7% vs 87%±9%,P<0.05);与IR组比较,CUR组CORT水平降低(102±18,P<0.05),海马BDNF含量增加(13.3±3.3,P<0.05),海马CA1区凋亡神经元数目减少(163±11,P<0.05),T迷宫正确率增高(79%±10%,P<0.05);与IR组比较,CORT组海马BDNF降低(4.4±1.2,P<0.05),海马CA1区凋亡神经元数目增加(332±35,P<0.05),T迷宫正确率降低(58%±6%,P<0.05);与CORT组比较,CUR+CORT组海马BDNF含量增加(10.5±2.3,P<0.05),海马CA1区凋亡神经元数目降低(211±27,P<0.05),T迷宫正确率增高(71%±12%,P<0.05)。结论: 姜黄素预先给药可通过抑制应激反应改善大鼠全脑缺血再灌注后空间工作记忆。

关键词: 脑, 再灌注损伤, 工作记忆, 应激, 姜黄素

Abstract: AIM: To investigate the ameliorative effect of curcumin pretreatment against impaired spatial working memory on global cerebral ischemia-reperfusion rats and to explore its mechanism. METHODS: After trained on a modified T-maze, 120 adult SD rats were randomly divided into 5 groups: SHAM group, cerebral ischemia-reperfusion group (IR group), Curcumin group (CUR group), corticosterone group (CORT group) and Curcumin+CORT group (CUR+CORT group). Rats were treated with drugs or vehicles 1 h before 10min global cerebral ischemia. Six rats in each group 7 days after reperfusion were tested in T-maze. Six rats in each group were sacrificed at 2 h,1, 3 and 7d after reperfusion and their serum or brains were harvested. TUNEL assays were performed using the in situ cell death detection kit to detect the apoptosis neurons of CA1 area. Levels of serum corticosterone and hippocampi brain-derived neurotrophic factor(BDNF) was detected using ELISA procedure. RESULTS: Compared with SHAM group, corticosterone levels in IR group was increased (164±36 vs 92±24,P<0.05),and BDNF in hippocampiwas decreased (8.7±2.8 vs 19.4±5.1,P<0.05), apoptotic neurons in CA1 areas was increased (233±22 vs 21±4,P<0.01), and percentage of T-maze correct responses was decreased (65%±7% vs 87%±9%,P<0.05). Compared with IR group, serum corticosterone levels in CUR group was decreased (102±18, P<0.05), BDNF in hippocampi was increased (13.3±3.3, P<0.05), apoptotic neurons in CA1 areas was decreased (163±11, P<0.05), and percentage of T-maze correct responses was increased (79%±10%, P<0.05). Compared with IR group, CORT group hippocampi BDNF levels was decreased(4.4±1.2, P<0.05), apoptotic neurons in CA1 areas was increased(332±35, P<0.05), and percentage of T-maze correct responses was decreased(58%±6%, P<0.05). Compared with CORT group, hippocampi BDNF levels in CUR+CORT group was increased(10.5±2.3, P<0.05), apoptotic neurons in CA1 areas was decreased(211±27, P<0.05), and percentage of T-maze correct responses was increased (71%±12%, P<0.05). CONCLUSION: Curcumin pretreatment improves the impaired spatial working memory in global cerebral ischemia-reperfusion rats by inhibiting the stress response.

Key words: brain, reperfusion injury, working memory, stress, curcumin

中图分类号:

R965.2

姬斌, 刘绪华, 杨芳骅, 周瑞, 曹红, 李军. 姜黄素通过抗应激作用改善脑缺血再灌注大鼠工作记忆[J]. 中国临床药理学与治疗学, 2014, 19(12): 1321-1325.

JI Bin, LIU Xu-hua, YANG Fang-hua, ZHOU Rui, CAO Hong, LI Jun. Curcumin improves the impaired working memory in cerebral ischemia-reperfusion rats by inhibiting the stress response[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(12): 1321-1325.

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姜黄素通过抗应激作用改善脑缺血再灌注大鼠工作记忆

Curcumin improves the impaired working memory in cerebral ischemia-reperfusion rats by inhibiting the stress response

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