脑缺血再灌注损伤后神经细胞凋亡与褪黑素的影响

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (7): 740-743.

脑缺血再灌注损伤后神经细胞凋亡与褪黑素的影响

余涓¹, 周宇², 郑祥¹, 陈崇宏²

¹福建医科大学生理学与病理生理学系, ²药理学系, 福州 350004, 福建

收稿日期:2008-03-13 修回日期:2008-04-23 出版日期:2008-07-26 发布日期:2020-10-14
作者简介:余涓,女,副教授,硕士生导师,研究方向:脑血管疾病。Tel:0591-83569303 E-mail:tune9@163.com
基金资助:
福建省教育厅资助课题(01AO27)

Apoptosis of the neurocytes after cerebral ischemia-reperfusion injury and effects of melatonin

YU Juan¹, ZHOU Yu², ZHENG Xiang¹, CHEN Chong-hong²

¹Department of Physiology and Pathophysiology, ²Department of Pharmacology, Fujian Medical University, Fuzhou 350004, Fujian, China

Received:2008-03-13 Revised:2008-04-23 Online:2008-07-26 Published:2020-10-14

摘要/Abstract

摘要： 目的:观察局灶性脑缺血再灌注损伤(CIRI)后神经细胞凋亡与褪黑素(MT)的影响,探讨相关机制。方法:线栓法制作大鼠大脑中动脉闭塞2h/再灌注24h模型,再灌注0、1、2、6hi.p.MT。TTC染色观察脑梗死体积;TUNEL法检测神经细胞凋亡;免疫组化法检测脑组织Bcl-2和Bax蛋白表达;无机磷酸法测定脑组织钙调神经磷酸酶(CaN)活性;毛细管区带电泳(CZE)法测定脑组织ATP含量。结果:MT10、20mg/kg均可显著缩小脑梗死体积;MT20mg/kg可显著降低脑组织缺血半暗带区(IP)神经细胞凋亡、增高Bcl-2/Bax比值,显著抑制损伤侧脑组织CaN活性,升高脑组织ATP含量。结论:MT抑制CIRI后脑组织神经细胞凋亡,使脑梗死体积减小,其机制与上调Bcl-2/Bax比值、抑制CaN活性升高、增加ATP保有量均有关。

关键词: 脑缺血再灌注损伤, 褪黑素, 凋亡, Bcl-2/Bax, 钙调神经磷酸酶, ATP

Abstract: AIM: To observe apoptosis of the neurocytes after focal cerebral ischemia-reperfusion injury (CIRI) in the brain tissue of rats and the effects and mechanism of melatonin (MT).METHODS: The models with cerebral ischemicre-reperfusion were induced by intraluminal middle cerebral artery occlusion (MCAO) with a nylon monofilament suture, 2 h occlusion followed by 24 h reperfusion.MT was intraperitonealed after reperfusion for 0, 1, 2, 6 h.The volume of cerbral infarction was observed using 2, 3, 4-triphenyl tetrazolium chloride (TTC) dyeing, apoptosis of the neurocytes was detected with TUNEL technique, the expression levels of Bcl-2 and Bax proteinum in brain tissue were detected by immunohistochemistry technique, the calcineurin activation in brain tissue was determined by inorganic phosphate method, ATP contents in brain tissue were measured with capillary zone electrophoresis(CZE) method.RESULTS: Compared with the vehicle model, the volume of cerbral infarction was reduced significantly by 10, 20 mg/kg MT, apoptosis of the neurocytes of ischemia penumbra (IP) area in the brain tissue was depressed by 20 mg/kg MT, the ratio of Bcl-2/Bax proteinum expression was increased, and the calcineurin activation of brain tissue in injured side was inhibited significantly, ATP contents in brain tissue were advanced.CONCLUSION: MT can antagonize apoptosis of the neurocytes in brain tissue after CIRI, reduce the volume of cerbral infarction.The mechanism may be related with the ratio of up-regulation Bcl-2/Bax, advancing of calcineurin activation inhibition, increasing of the ATP capacity.

Key words: cerebral ischemia-reperfusion injury, melatonin, apoptosis, Bcl-2/Bax, calcineurin, ATP

中图分类号:

R965.2

余涓, 周宇, 郑祥, 陈崇宏. 脑缺血再灌注损伤后神经细胞凋亡与褪黑素的影响[J]. 中国临床药理学与治疗学, 2008, 13(7): 740-743.

YU Juan, ZHOU Yu, ZHENG Xiang, CHEN Chong-hong. Apoptosis of the neurocytes after cerebral ischemia-reperfusion injury and effects of melatonin[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(7): 740-743.

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