匹诺塞林对脑缺血再灌注内质网应激凋亡相关基因mRNA表达的影响

doi:10.12092/j.issn.1009-2501.2018.01.007

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (1): 34-40.doi: 10.12092/j.issn.1009-2501.2018.01.007

匹诺塞林对脑缺血再灌注内质网应激凋亡相关基因mRNA表达的影响

武彩霞¹，杜冠华²

¹山东医学高等专科学校，临沂 276000，山东；²中国医学科学院药物研究所&北京协和医学院，药物靶点研究与药物筛选北京市重点实验室，北京 100050

收稿日期:2017-08-15 修回日期:2017-10-10 出版日期:2018-01-26 发布日期:2018-02-07
通讯作者: 杜冠华，男，博士生导师，研究员，主要从事神经药理学与新药发现研究。 Tel: 010-63165184 E-mail：dugh@imm.ac.cn
作者简介:武彩霞，女，博士研究生，副教授，主要从事药理学教学与科研工作。 Tel: 0539-6173385 E-mail：sdyx91@126.com
基金资助:
山东省医药卫生科技发展计划项目（2016WS0566）

Effects of pinocembrin on mRNA expression of genes related to endoplasmic reticulum stress-mediated apoptosis in acute injury induced by focal cerebral ischemia-reperfusion

WU Caixia¹, DU Guanhua²

¹ Shandong Medical College, Linyi 276002, Shandong,China；² National Centre for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China

Received:2017-08-15 Revised:2017-10-10 Online:2018-01-26 Published:2018-02-07

摘要/Abstract

摘要：

目的: 观察匹诺塞林对大鼠脑缺血再灌注急性期损伤内质网应激凋亡途径相关基因的调控作用。方法: 雄性SD大鼠50只，阻塞大脑中动脉建立脑缺血再灌注模型，随机分为假手术组、模型组、匹诺塞林1 mg/kg组、3 mg/kg组和10 mg/kg组，其中模型组及匹诺塞林各给药组，分别于大脑中动脉阻塞2 h后再灌注同时给药，6 h后取血并断头取脑，取缺血半暗带组织，实时荧光定量PCR（RT-PCR）法测定GRP78、CHOP、ATF4、XBP-1的mRNA变化。结果: 匹诺塞林能增加急性局灶性脑缺血再灌注GRP78 mRNA水平，其中匹诺塞林3 mg/kg、10 mg/组与模型组比较，差异有统计学意义（P<0.05或P<0.01）；匹诺塞林能降低内质网应激凋亡相关蛋白CHOP、ATF4，XBP-1 mRNA水平，与模型组相比，差异有统计学意义（P<0.05或P<0.01）。结论: 匹诺塞林能抗脑缺血再灌注损伤，其机制可能与保护内质网功能，减少GRP78、CHOP、ATF4及XBP-1相关基因表达有关。

关键词: 匹诺塞林, 内质网应激, 脑缺血再灌注, GRP78, CHOP, ATF4, XBP-1

Abstract:

AIM: To investigate the effects of pinocembrin on mRNA expression of several genes related to endoplasmic reticulum stress-mediated apoptosis in acute injury induced by focal cerebral ischemia-reperfusion. METHODS: Fifty male Sprague-Dawley rats, weighing 260-280 g were divided into five groups: sham operation group; I/R group; I/R + pinocembrin (1, 3 and 10 mg/kg) group. Focal cerebral I/R model was established by occlusion of the middle cerebral artery(MCAO) for 2 h followed by 6 h reperfusion. Pinocembrin was administered intravenously at different doses at the onset of reperfusion. The mRNA expression of gene GRP78, CHOP, ATF4, XBP-1 was then detected by RT-PCR method in penumbra cortex, respectively. RESULTS: Pinocembrin significantly modulated the levels of mRNA expression of these genes by increasing GRP78 and attenuating CHOP expression along with ATF4, and XBP-1 (P<0.05 or P<0.01). CONCLUSION: Pinocembrin can protect against I/R injury, and the possible mechanism might be attributed to its regulation of mRNA expression of genes related to endoplasmic reticulum stress-mediated apoptosis in penumbra area.

Key words: pinocembrin, endoplasmic reticulum stress, focal cerebral ischemia reperfusion, GRP78, CHOP, ATF4, XBP-1

中图分类号:

R965.2

武彩霞，杜冠华. 匹诺塞林对脑缺血再灌注内质网应激凋亡相关基因mRNA表达的影响[J]. 中国临床药理学与治疗学, 2018, 23(1): 34-40.

WU Caixia, DU Guanhua. Effects of pinocembrin on mRNA expression of genes related to endoplasmic reticulum stress-mediated apoptosis in acute injury induced by focal cerebral ischemia-reperfusion[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(1): 34-40.

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匹诺塞林对脑缺血再灌注内质网应激凋亡相关基因mRNA表达的影响

Effects of pinocembrin on mRNA expression of genes related to endoplasmic reticulum stress-mediated apoptosis in acute injury induced by focal cerebral ischemia-reperfusion

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