1,8-cineole ameliorates ischaemic brain damage via TRPC6/CREB pathways in rats.
1,8-cineole ameliorates ischaemic brain damage via TRPC6/CREB pathways in rats.
复制标题
DOI：
10.1093/jpp/rgab035
复制
发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Chen Meng;Wenjing Zeng;Jing Lv;Yu Wang;Meiling Gao;Ruijie Chang;Qing Li;Xianyu Wang
中科院分区：
文献类型：
--
作者：
Chen Meng;Wenjing Zeng;Jing Lv;Yu Wang;Meiling Gao;Ruijie Chang;Qing Li;Xianyu Wang
先前的一项体外研究报道了氧化单萜1,8-桉叶油脑（桉叶油脑）在培养中减弱氧-葡萄糖剥夺/再氧化引起的神经元。然而，到目前为止，没有活体证据表明桉树脑对中风有神经保护作用。本研究旨在探讨桉树脑是否能减轻大鼠脑缺血损伤。方法建立大鼠大脑中动脉闭塞（MCAO）模型，再灌注24 h。雄性大鼠连续7天口服桉树脑（100 mg/kg），然后进行MCAO手术。在缺血脑组织中测量梗死体积、神经功能缺损、细胞凋亡和145 kDa （SBDP145）、瞬时受体电位规范（亚型）6 （TRPC6）和磷酸化CREB （p-CREB）的全谱蛋白分解产物的表达水平。与载药治疗相比，桉树脑治疗显著减少MCAO大鼠梗死体积、神经功能障碍、神经元凋亡、SBDP145形成和TRPC6降解，并增强p-CREB表达。这些神经保护作用被MEK或CaMKIV信号的药理抑制明显抑制。结论：本研究提供的体内证据表明，桉树脑预处理可减轻缺血性卒中引起的脑损伤，主要通过阻断calpain诱导的TRPC6降解，并通过MEK/CREB和CaMKIV/CREB信号通路激活CREB。
OBJECTIVES A previous in vitro study reported that the monoterpene oxide 1,8-cineole (cineole) attenuates neuronal caused by oxygen-glucose deprivation/reoxygenation in culture. However, to date, there is no in vivo evidence showing neuroprotective effects of cineole against stroke. This study aimed to investigate whether cineole attenuates cerebral ischaemic damage in rats. METHODS A rat model of middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion was applied. Male rats were treated with oral cineole (100 mg/kg) for 7 consecutive days, then subjected to MCAO surgery. Infarct volume, neurologic deficits, apoptosis and expression levels of all-spectrin breakdown products of 145 kDa (SBDP145), transient receptor potential canonical (subtype) 6 (TRPC6) and phosphorylated CREB (p-CREB) were measured in ischaemic brain tissues. KEY FINDINGS Cineole treatment significantly reduced infarct volume, neurological dysfunction, neuronal apoptosis, SBDP145 formation and TRPC6 degradation and enhanced p-CREB expression in MCAO rats compared with vehicle treatment. These neuroprotective effects were markedly suppressed by pharmacological inhibition of MEK or CaMKIV signalling. CONCLUSIONS Our study provides in vivo evidence demonstrating that cineole pretreatment attenuates ischaemic stroke-induced brain damage, mainly through blocking calpain-induced TRPC6 degradation and activating CREB via MEK/CREB and CaMKIV/CREB signalling pathways.