Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Institute of Anesthesiology, Hubei University of Medicine, Shiyan, Hubei, China.
J Pharm Pharmacol. 2021 Jun 8;73(7):979-985. doi: 10.1093/jpp/rgab035.
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.
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.
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.
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.
先前的一项体外研究表明，单萜氧化物 1,8-桉叶油醇（桉油醇）可减轻培养物中氧葡萄糖剥夺/再氧合引起的神经元损伤。然而，迄今为止，尚无体内证据表明桉油醇对中风具有神经保护作用。本研究旨在探讨桉油醇是否可减轻大鼠脑缺血损伤。
应用大脑中动脉闭塞（MCAO）后 24 小时再灌注的大鼠模型。雄性大鼠连续 7 天给予口服桉油醇（100mg/kg），然后进行 MCAO 手术。测量缺血脑组织中的梗死体积、神经功能缺损、细胞凋亡以及全 spectrin 断裂产物 145kDa（SBDP145）、瞬时受体电位经典（亚型）6（TRPC6）和磷酸化 CREB（p-CREB）的表达水平。
与载体处理相比，桉油醇处理可显著减少 MCAO 大鼠的梗死体积、神经功能障碍、神经元凋亡、SBDP145 形成和 TRPC6 降解，并增强 p-CREB 的表达。MEK 或 CaMKIV 信号通路的药理学抑制明显抑制了这些神经保护作用。
本研究提供了体内证据，表明桉油醇预处理可减轻缺血性中风引起的脑损伤，主要通过阻断钙蛋白酶诱导的 TRPC6 降解并通过 MEK/CREB 和 CaMKIV/CREB 信号通路激活 CREB。
