急性给予β-石竹烯可预防短暂性颈总动脉闭塞和再灌注期间内源性大麻素系统的激活。
Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion.
机构信息
Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, (CA), 09042, Italy.
出版信息
Lipids Health Dis. 2018 Feb 5;17(1):23. doi: 10.1186/s12944-018-0661-4.
BACKGROUND
The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) has been shown to stimulate early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The aim of the present study is to probe the possibility to prevent the molecular changes induced by the BCCAO/R with dietary natural compounds known to possess anti-inflammatory activity, such as the phytocannabinoid beta-caryophyllene (BCP).
METHODS
Two groups of adult Wistar rats were used, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half of the rats were gavage-fed with a single dose of BCP (40 mg/per rat in 300 μl of sunflower oil as vehicle), while the second half were pre-treated with the vehicle alone. HPLC, Western Blot and immunohistochemistry were used to analyze cerebral cortex and plasma.
RESULTS
After BCCAO/R, BCP prevented the increase of lipoperoxides occurring in the vehicle-treated rats in both cerebral cortex and plasma. In the frontal cortex, BCP further prevented activation of the endocannabinoid system (ECS), spared the docosahexaenoic acid (DHA), appeared to prevent the increase of cyclooxygenase-2 and increased the peroxisome-proliferator activated receptor-alpha (PPAR-alpha) protein levels, while, in plasma, BCP induced the reduction of arachidonoylethanolamide (AEA) levels as compared to vehicle-treated rats.
CONCLUSIONS
Collectively, the pre-treatment with BCP, likely acting as agonist for CB2 and PPAR-alpha receptors, modulates in a beneficial way the ECS activation and the lipoperoxidation, taken as indicative of oxidative stress. Furthermore, our results support the evidence that BCP may be used as a dietary supplement to control the physiological response to the hypoperfusion/reperfusion-induced oxidative stress.
背景
通过诱导双侧颈总动脉闭塞再灌注（BCCAO/R）实现的短暂性全脑低灌注/再灌注已被证明可刺激早期分子变化，这些变化在脑组织和血浆中很容易被追踪，并表明组织对再灌注诱导的氧化应激和炎症的生理反应。本研究的目的是探讨用具有抗炎活性的膳食天然化合物（如植物大麻素β-石竹烯（BCP））预防 BCCAO/R 诱导的分子变化的可能性。
方法
使用两组成年 Wistar 大鼠，假手术组和 BCCAO/R 组。在两组中，手术前 6 小时，一半大鼠给予 BCP 单次剂量（40mg/只大鼠，用 300μl 葵花籽油作为载体），另一半给予载体单独预处理。使用 HPLC、Western Blot 和免疫组织化学分析大脑皮质和血浆。
结果
在 BCCAO/R 后，BCP 可防止在载体处理的大鼠中发生的大脑皮质和血浆中脂过氧化物的增加。在额皮质中，BCP 进一步防止内源性大麻素系统（ECS）的激活，保护二十二碳六烯酸（DHA），似乎防止环加氧酶-2 的增加，并增加过氧化物酶体增殖物激活受体-α（PPAR-α）蛋白水平，而在血浆中，BCP 诱导与载体处理的大鼠相比，花生四烯酸乙醇酰胺（AEA）水平降低。
结论
总之，BCP 的预处理可能作为 CB2 和 PPAR-α 受体的激动剂，以有益的方式调节 ECS 的激活和脂过氧化，作为氧化应激的指标。此外，我们的结果支持 BCP 可作为膳食补充剂用于控制对低灌注/再灌注诱导的氧化应激的生理反应的证据。
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