姜黄素对高血压病大鼠全脑缺血再灌注时海马神经元损伤及皮质酮、SGK1表达的影响

doi:10.12092/j.issn.1009-2501.2019.07.003

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (7): 737-743.doi: 10.12092/j.issn.1009-2501.2019.07.003

姜黄素对高血压病大鼠全脑缺血再灌注时海马神经元损伤及皮质酮、SGK1表达的影响

俞陈陈¹，刘树群¹，刘建龙¹，曹红²，刘雪娇¹，蔡茜茜¹

¹温州医科大学附属第一医院麻醉科，²温州医科大学附属第二医院麻醉科，温州 325015，浙江

收稿日期:2018-12-27 修回日期:2019-06-20 出版日期:2019-07-26 发布日期:2019-07-29
通讯作者: 曹红，女，硕士，教授，研究方向：围术期重要器官保护。 Tel:13758497562 E-mail: caohongwz@163.com
作者简介:俞陈陈，女，硕士，医师，研究方向：围术期重要器官保护。 Tel:18267737578 E-mail:57298871@qq.com
基金资助:
国家自然科学基金资助项目（81073125）；浙江省科技厅资助项目（2011C23022）

Effects of curcumin on injury in hippocampal neurons and expression of blood corticosterone and SGK1 in hippocampal during global cerebral ischemia-reperfusion injury in hypertensive rats

YU Chenchen¹, LIU Shuqun¹, LIU Jianlong¹, CAO Hong², LIU Xuejiao¹, CAI Xixi¹

¹Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, Zhejiang, China; ² Department of Anesthesiology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, Zhejiang, China

Received:2018-12-27 Revised:2019-06-20 Online:2019-07-26 Published:2019-07-29

摘要/Abstract

摘要：

目的:探讨姜黄素对高血压病大鼠全脑缺血再灌注时海马神经元损伤及血清皮质酮、海马血清和糖皮质激素诱导激酶1（serum-and glucocorticoid-inducible kinases1，SGK1）表达的影响。方法:雄性Wistar-Kyoto（WKY）大鼠和自发性高血压病（SH）大鼠，随机分为5组：假手术组（W-Sham、S-Sham）、缺血再灌注组（W-IR、S-IR）和姜黄素组（S-Cur）。各组按再灌注时间分为3 h、12 h、1 d、3 d和7 d 5个时间点。采用四血管阻断法制备全脑缺血再灌注模型（缺血10 min后恢复灌注），HE染色观察海马CA1区神经细胞形态，Nissl染色计数海马CA1区平均锥体细胞密度，ELISA法检测血清皮质酮及海马SGK1，于再灌注后7 d观察行为学。结果:与假手术组比较，缺血再灌注组学习和记忆能力下降，海马CA1区神经元损伤加重，血清皮质酮水平增加，海马SGK1表达上调（P<0.05）；与W-IR组比较，S-IR组学习和记忆能力下降，海马CA1区神经元损伤加重，血清皮质酮水平增加（P<0.05），海马SGK1蛋白表达下调（P<0.05）；姜黄素组学习和记忆能力明显改善，海马CA1区神经元损伤减轻，血清皮质酮水平下降（P<0.05），海马SGK1蛋白表达上调（P<0.05）。结论:姜黄素减轻高血压病大鼠全脑缺血再灌注海马神经元损伤的机制可能与抑制皮质酮、上调SGK1表达有关。

关键词: 姜黄素, 全脑缺血再灌注, 认知功能, 皮质酮, 血清和糖皮质激素诱导激酶1

Abstract:

AIM: To investigate the effects of curcumin on injury in hippocampal neurons and expression of blood corticosterone and serum-and glucocorticoid-inducible kinases1（SGK1） in hippocampal during global cerebral ischemia-reperfusion injury in hypertensive rats. METHODS: Male Wistar-Kyoto rats and male spontaneously hypertensive rats were randomLy divided into five groups (n=30): sham group (W-Sham and S-Sham), ischemia-reperfusion group (W-IR and S-IR), curcumin group (S-Cur). Rats were sacrificed at 3 h, 12 h, 1 d, 3 d, 7 d after reperfusion. Global brain ischemic model was established by 4-VO method. HE Staining was used to observe the vertebral cell morphology in hippocampal CA1 region. Nissl Stainning was applied to detect the average density of vertebral cell in hippocampal CA1 region. The corticosterone in blood and SGK1 in hippocampal were determined by ELISA. At 7d after reperfusion the behavior of the rats was observed. RESULTS:Compared with sham group , the ability to learn and remember was greatly decreased in ischemia-reperfusion group, the number of injured neurons was significantly enhanced , the corticosterone in blood was extremely enhanced（P<0.05）, the expression of SGK1 in hippocampal was significantly increased（P<0.05）. Compared with W-IR, the ability of S-IR to learn and remember was greatly decreased, the number of injured neurons was extremely enhanced, the corticosterone in blood was significantly increased（P<0.05）, the expression of SGK1 in hippocampal was significantly decreased（P<0.05）. The number of injured neurons was greatly declined in S-Cur, the ability to learn and remember was improved , the corticosterone in blood was extremely decreased（P<0.05）, the expression of SGK1 in hippocampal was significantly increased（P<0.05）. CONCLUSION: Inhibition of corticosterone in blood and overexpression of SGK1 in hippocampus may be involved in the mechanism by which curcumin reduces global cerebral IR injuty in hypertensive rats.

Key words: curcumin, cerebral ischemia/reperfusion, cognitive function, corticosterone, serum-and glucocorticoid-inducible kinases1

中图分类号:

R965.2

俞陈陈，刘树群，刘建龙，曹红，刘雪娇，蔡茜茜. 姜黄素对高血压病大鼠全脑缺血再灌注时海马神经元损伤及皮质酮、SGK1表达的影响[J]. 中国临床药理学与治疗学, 2019, 24(7): 737-743.

YU Chenchen, LIU Shuqun, LIU Jianlong, CAO Hong, LIU Xuejiao, CAI Xixi. Effects of curcumin on injury in hippocampal neurons and expression of blood corticosterone and SGK1 in hippocampal during global cerebral ischemia-reperfusion injury in hypertensive rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(7): 737-743.

参考文献

［1］余结根, 李荣, 梁伟, 等. 醒脑静治疗高血压脑出血的Meta分析［J］.中国临床药理学与治疗学, 2016, 21(4): 417-424.
［2］Grell AS, Mostajeran M, Edvinsson L, et al. Contractile responses in spontaneously hypertensive rats after transient middle cerebral artery occlusion［J］. Pharmacology, 2018, 101(3/4): 120-132.
［3］Ganzer CA，Barnes A，Uphold C, et al.Transient ischemic attack and cognitive impairment: a review［J］. J Neurosci Nurs，2016, 48(6): 322-327.
［4］Sundar Dhilip Kumar S, Houreld NN, Abrahamse H, et al. Therapeutic potential and recent advances of curcumin in the treatment of aging-associated diseases［J］.Molecules, 2018, 23(4): 835-837.
［5］叶克平, 陈春茹, 郑晋伟, 等. 姜黄素对自发性高血压大鼠海马缺血/再灌注损伤神经元凋亡核通路的影响［J］. 中国应用生理学杂志, 2010, 26(4): 416-423.
［6］Pulsinelli WA, Brierley JB. A new model of bilateral hemispheric ischemia in the unanesthetized rat［J］. Stroke, 1979, 10(3): 267-272.
［7］Tayebati SK, Tomassoni D, Amenta F.Spontaneously hypertensive rat as a model of vascular brain disorder: microanatomy, neurochemistry and behavior［J］. J Neurol Sci, 2012, 322(1/2): 241-249.
［8］汪小丹, 沈露露, 俞陈陈, 等.姜黄对高血压病大鼠全脑缺血再灌注损伤时海马炎性反应的影响［J］.中华麻醉学杂志, 2014, 34(6): 753-757.
［9］Franco AJ, Chen C, Scullen T, et al.Sensitization of the hypothalamic-pituitary-adrenal axis in a male rat chronic stress model［J］. Endocrinology, 2016, 157(6): 2346-2355.
［10］Semyachkina-Glushkovskaya O, Shirokov A, Gekalyuk A, et al.Stress plays provoking role in hypertension-related stroke: injuries of blood-brain barrier function［C］.Asia Communications and Photonics Conference, 2016, as1k3.
［11］Barra de la Tremblaye P, Plamondon H.Alterations in the corticotropin-releasing hormone (CRH) neurocircuitry: Insights into post stroke functional impairments［J］. Front Neuroendocrinol,2016, 42(10): 53-75.
［12］Joёls M.Functional actions of cortiecosteroids in the hippocampus［J］. Eur J Pharmacol, 2008, 583(2/3): 312-321.
［13］朱洁瑾, 吴湧, 叶晓莉, 等.漆黄素对脑缺血再灌注诱导学习记忆损伤及HPA轴的影响［J］.中国临床药理学与治疗学, 2017, 22(9):1002-1007.
［14］Talarico C, Dattilo V, D'Antona L, et al. SGK1, the new player in the game of resistance: chemo-radio molecular target and strategy for inhibition［J］. Cell Physiol Biochem, 2016, 39(5): 1863-1876.
［15］Anacker C, Cattaneo A, Musaelyan K, et al. Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis［J］. Proc Natl Acad Sci USA, 2013,110(21): 8708-8713.
［16］Hinds LR, Chun LE, Woodruff ER, et al.Dynamic glucocorticoid-dependent regulation of Sgk1 expression in oligodendrocytes of adult male rat brain by acute stress and time of day［J］. PLoS One, 2017, 12(4): e0175075.
［17］Xie Y, Jiang D, Xiao J, et al.Ischemic preconditioning attenuates ischemia/reperfusion-induced kidney injury by activating autophagy via the SGK1 signaling pathway［J］. Cell Death Dis, 2018, 9(3): 338.
［18］Zhang W, Qian Cy, Li SQ. Protective effect of SGK1 in rat hippocampal neurons subjected to ischemia reperfusion［J］. Cell Physiol Biochem, 2014, 34(2): 299-312.
［19］俞陈陈, 胡涵, 汪小丹, 等.姜黄素对自发性高血压大鼠脑缺血/再灌注后海马神经元损伤及RANTES表达的影响［J］. 中国应用生理学杂志, 2014, 30(4): 340-344.
［20］姬斌, 刘绪华, 杨芳骅, 等.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.

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姜黄素对高血压病大鼠全脑缺血再灌注时海马神经元损伤及皮质酮、SGK1表达的影响

Effects of curcumin on injury in hippocampal neurons and expression of blood corticosterone and SGK1 in hippocampal during global cerebral ischemia-reperfusion injury in hypertensive rats

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