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β-榄香烯通过抗氧化和抗细胞凋亡机制减轻大鼠脑缺血/再灌注损伤。

Germacrone attenuates cerebral ischemia/reperfusion injury in rats via antioxidative and antiapoptotic mechanisms.

机构信息

Department of Pediatrics, Xiangya Hospital of Central South University, Changsha, Hunan, China.

Department of Nephrology and Rheumatology, Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, Hunan, China.

出版信息

J Cell Biochem. 2019 Nov;120(11):18901-18909. doi: 10.1002/jcb.29210. Epub 2019 Jul 18.

DOI:10.1002/jcb.29210
PMID:31318092
Abstract

Germacrone (GM) is an anti-inflammatory compound extracted from Rhizoma curcuma. Here, we strived to investigate the neuroprotective effects of GM in rat models of transient middle cerebral artery occlusion/reperfusion injury. Rats immediately after cerebral ischemia were intraperitoneally injected with GM at doses of 5, 10, and 20 mg/kg. After 1 day of reperfusion, the water content in the brain, infarct volume, and neurological deficits were assessed. Hippocampus neurons were histopathologically examined by hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Activities of glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-PX) in brain tissue were detected. Real-time PCR and Western blotting were utilized to quantify the expression of apoptosis markers, such as caspase-3, Bax, and Bcl-2. The content of phospho-Akt (p-Akt) was also measured using Western blotting. GM treatment markedly decreased the brain water content, infarct volume and the neurological deficits, which was corroborated by attenuated histopathologic change. MDA levels were reduced and activities of GSH, SOD, and GSH-PX were elevated after GM treatment. Caspase-3 and Bax were decreased, and Bcl-2 was increased at both messenger RNA and protein levels by GM treatment. The p-Akt expression was increased by GM. Our data indicated that the neuroprotective effects of GM may attenuate the injuries from cerebral ischemia/reperfusion in rats through antioxidative and antiapoptotic mechanisms.

摘要

莪术倍半萜醇(GM)是一种从莪术根茎中提取的抗炎化合物。在这里,我们旨在研究 GM 在大鼠短暂性大脑中动脉闭塞/再灌注损伤模型中的神经保护作用。脑缺血后立即给大鼠腹腔内注射 GM,剂量分别为 5、10 和 20mg/kg。再灌注 1 天后,评估脑含水量、梗死体积和神经功能缺损。用苏木精和伊红染色和末端脱氧核苷酸转移酶 dUTP 缺口末端标记染色对海马神经元进行组织病理学检查。检测脑组织中谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-PX)的活性。利用实时 PCR 和 Western blot 定量检测凋亡标志物,如 caspase-3、Bax 和 Bcl-2 的表达。还使用 Western blot 测量磷酸化 Akt(p-Akt)的含量。GM 治疗显著降低了脑含水量、梗死体积和神经功能缺损,这与组织病理学变化减弱相符。GM 治疗后 MDA 水平降低,GSH、SOD 和 GSH-PX 的活性升高。GM 治疗后 caspase-3 和 Bax 减少,Bcl-2 在信使 RNA 和蛋白质水平上均增加。GM 增加了 p-Akt 的表达。我们的数据表明,GM 的神经保护作用可能通过抗氧化和抗细胞凋亡机制减轻大鼠脑缺血/再灌注损伤。

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