The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China.
Int J Mol Sci. 2022 Dec 29;24(1):544. doi: 10.3390/ijms24010544.
Endoplasmic reticulum (ER) stress plays an important role in cerebral ischemia-reperfusion injury (CIRI). Geraniol has antioxidant, antibacterial, and anti-inflammatory activities. Studies have shown that geraniol has a protective effect against CIRI in rats, but the exact mechanism is unclear. Purpose: The aim of this study was to investigate the protective mechanism of geraniol against CIRI. We established a middle cerebral artery occlusion reperfusion model in rats and a PC12 cell oxygen-glucose deprivation/reoxygenation (OGD/R) model to observe the neuroprotective effects of geraniol. Neurological scoring, 2,3,5-triphenyltetrazolium chloride staining, and hematoxylin and eosin staining were used to evaluate the neuroprotective effects of geraniol against CIRI. ER-stress-related and apoptosis-related protein expression was detected via Western blotting and immunofluorescence. Apoptosis was also detected via TUNEL assays and flow cytometry. The fluorescent detection of intracellular calcium was achieved using fluorescent calcium-binding dyes, and transmission electron microscopy was used to assess the neuronal ultrastructure. Geraniol effectively attenuated cerebral infarction and pathological injury after CIRI, had a protective effect against CIRI, significantly reduced the expression of the ER-stress-related proteins P-PERK, ATF4, CHOP, and GRP78 and the pro-apoptotic protein BAX, increased the expression of the anti-apoptotic protein BCL-2, and reduced the occurrence of apoptosis. In the OGD/R model in PC12 cells, the protective effect of geraniol was the same as that in vivo. Our results suggest that geraniol has a protective effect against ischemic stroke by a mechanism possibly related to ER stress via the PERK-ATF4-CHOP pathway.
内质网（ER）应激在脑缺血再灌注损伤（CIRI）中起重要作用。香叶醇具有抗氧化、抗菌和抗炎活性。研究表明，香叶醇对大鼠 CIRI 具有保护作用，但确切机制尚不清楚。目的：本研究旨在探讨香叶醇对 CIRI 的保护机制。我们建立了大鼠大脑中动脉闭塞再灌注模型和 PC12 细胞氧葡萄糖剥夺/复氧（OGD/R）模型，观察香叶醇的神经保护作用。神经功能评分、2,3,5-三苯基四氮唑氯化物染色和苏木精-伊红染色用于评价香叶醇对 CIRI 的神经保护作用。通过 Western blot 和免疫荧光检测 ER 应激相关和凋亡相关蛋白的表达。通过 TUNEL 检测和流式细胞术检测细胞凋亡。通过荧光钙结合染料检测细胞内钙荧光，通过透射电子显微镜评估神经元超微结构。香叶醇可有效减轻 CIRI 后的脑梗死和病理损伤，对 CIRI 具有保护作用，显著降低 ER 应激相关蛋白 P-PERK、ATF4、CHOP 和 GRP78 及促凋亡蛋白 BAX 的表达，增加抗凋亡蛋白 BCL-2 的表达，减少凋亡的发生。在 PC12 细胞的 OGD/R 模型中，香叶醇的保护作用与体内相同。我们的结果表明，香叶醇通过 PERK-ATF4-CHOP 通路可能与 ER 应激有关，对缺血性中风具有保护作用。
