藏红素在体保护大鼠脑缺血/再灌注损伤和可能的作用机制（英文）  

Crocin protects against rat brain ischemia-reperfusion injury in vivo and the studies on certain aspects of the mechanisms involved

作　　者：王日康 张浪[4] 陈河如 WANG Rikang;ZHANG Lang;CHEN Heru(Shenzhen Key Laboratory for Anti-Ageing and Regenerative Medicine,Health Science Center,Shenzhen University,Shenzhen 518060,China;Institute of Traditional Chinese Medicine and Natural Products,College of Pharmacy,Jinan University,Guangzhou 510632,China;National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine,Jiangxi University of Traditional Chinese Medicine,Nanchang 330006,China;Chinese People s Liberation Army No.94 Hospital,Nanchang 330006,China)

机构地区：[1]深圳大学医学部∥深圳市抗衰老和再生医学重点实验室,广东深圳518060 [2]暨南大学药学院中药及天然药物研究所,广东广州510632 [3]江西中医药大学中药固体制剂制造技术国家工程研究中心,江西南昌330006 [4]中国人民解放军第94医院,江西南昌330006

出　　处：《中山大学学报（自然科学版）》2018年第2期143-154,共12页Acta Scientiarum Naturalium Universitatis Sunyatseni

基　　金：国家自然科学基金(81560662);中国博士后基金(2017M610543)

摘　　要：通过中脑冠状动脉闭塞(MCAO)造成缺血/再灌注(I/R)损伤大鼠模型。藏红素预处理可以剂量依赖性地改善I/R损伤所造成的神经性机能障碍和降低脑梗死体积。免疫印迹分析显示藏红素能够上调MCAO大鼠大脑海马中Bcl-2的表达,下调Bax和Caspase-3的表达。由于氧化/硝化应激在I/R损伤中相当重要,建立了硝普钠(SNP)-诱导损伤的PC12细胞模型来模拟在I/R大脑中大量释放一氧化氮(NO)造成的神经毒性。研究结果与藏红素保护MCAO大鼠造成海马损伤一致,藏红素显著下调SNP-损伤PC12细胞所引起LDH和ROS水平的升高,并且剂量依赖性下调促凋亡蛋白Bax,Caspase-3和cytochrome c水平的升高,而上调抗凋亡蛋白Bcl-2蛋白的表达。所有证据表明,藏红素是一种可能通过调控凋亡蛋白活性及线粒体机能障碍机制有效保护I/R损伤的药物。Crocin pretreatment markedly improved the neurological dysfunction and decreased the infarct volume in a dose-dependent manner in middle cerebral artery occlusion(MCAO)rats.Western blot analysis showed that crocin up-regulated B-cell lymphoma 2(Bcl-2)expression,down-regulated Bcl-2 associated protein X(Bax)and cleaved caspase-3 expression of hippocampus in MCAO rats.Because oxidative/nitrative stress is a very important factor in ischemia-reperfusion(I/R)injury,thus,a sodium nitroprusside(SNP)-impaired PC12 cell model was set up to mimick nitric oxide(NO)excitotocixity in I/R brain.The results showed that crocin protected PC12 cells against SNP-induced cytotoxicity via attenuating the caspase activation and mitochondrial dysfunction in vitro.Crocin significantly attenuated apoptosis,lactate dehydrogenase(LDH)release,caspase-3 activation,mitochondria membrane potential corruption and the intracellular accumulation of ROS induced by SNP in PC12 cells.Moreover,SNP decreased the expression level of Bcl-2,induced the expression of cytochrome c and Bax in PC12 cells,which is similar to the case of hippocampus in MCAO rats;and crocin reversed all these effects.All these evidences support that crocin is an effective agent to protect I/R injury via reasonable mechanism.

关 键 词：藏红素 大脑缺血 缺血再灌注(I/R) 氧化/硝化应激 凋亡 硝普钠 

分 类 号：R965[医药卫生—药理学]