欢迎访问《解剖学报》官方网站！今天是
English
油橄榄叶提取物干预海洛因依赖小鼠认知和氧化损伤及细胞凋亡的变化
Olive leaf extract improves cognition and reduces oxidative damage and apoptosis in mice with heroin dependence
目的 探讨油橄榄叶提取物（OLE）对海洛因依赖小鼠认知和氧化损伤及细胞凋亡的影响。方法 150只小鼠皮下注射海洛因（10 mg/ kg）40 d，再分别给予不同剂量的（0、50、100、200 mg/kg）的OLE进行皮下注射治疗，用Morris水迷宫观察空间学习记忆能力的变化，用透射电子显微镜观察海马细胞结构的改变，用比色法检测小鼠海马超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化酶（GPx）、还原型谷胱甘肽（GSH）的活性及丙二醛（MDA）的含量，免疫组织化学和Western blotting检测海马Bax蛋白和Caspase-3的表达。 结果 模型组小鼠海马神经元核膜不规则，细胞器结构异常或空泡化，小鼠逃避潜伏期和逃避的距离高于正常组，在目标象限探索的时间及游泳距离占总距离的百分比低于正常组（P<0.01），海马组织SOD、CAT、GPx、GSH活性低于正常组，MDA含量高于正常组（P<0.01），海马组织Bax蛋白和caspase-3的表达高于正常组（P<0.01）。OLE治疗组小鼠海马神经元损害程度减轻，小鼠逃避潜伏期和逃避的距离缩短，在目标象限探索的时间及游泳距离占总距离的百分比延长，海马组织SOD、CAT、GPx、GSH活性又升高，MDA含量及Bax蛋白和Caspase-3的表达又显著降低（P<0.05或P<0.01）。 结论 OLE对海洛因诱导的脑损伤的神经保护与其具有抗氧化能力。抑制细胞凋亡的特性有一定的关系。
Objective To observe the effect of olive leaves extract (OLE) on cognition, oxidative damage and hippocampal apoptosis in heroin-dependent mice. Methods One hundred and fifty mice were given subcutaneous administration of heroin (10 mg/ kg) for 40 days, and then treated with different doses (0, 50, 100, 200 mg/kg) of OLE. The spatial learning and memory abilities were evaluated with Morris water maze test. Changes of the cell structure of hippocampus were observed by transmission electron microscopy. Spectrophotometry was used to detect the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and malondialdehyde (MDA) content. Bax protein and caspase-3 expression in the hippocampus were determined by immunohistochemical and Western blotting analysis. Results Hippocampal neurons in the model group showed irregularity of nuclear membrane, abnormal or vacuolar structures of organelles. The escape latency and escape distances in the model group were significantly longer and the time spent and swimming distance percentage in the target quadrant were significantly shorter than that in the normal control group (P<0.01). The activities of SOD, CAT, GPx, and GSH in the model group lower than those of the normal control group, while the content of MDA was higher than that of normal control group (P<0.01). The expressions of Bax protein and Caspase-3 in the hippocampus of the model group were increased compared with the normal control group (P<0.01). Administration of OLE alleviated neuronal injuries and reduced damage to organells, and shortened the escape latency and escape distances, prolonged the time spent and swimming distance percentage in the target quadrant. Moreover, the activities of SOD, CAT, GPx, and GSH in OLEtreated groups increased, while the MDA content and expressions of Bax protein and Caspase-3 decreased, in a dose-dependent manner (P<0.05 or P<0.01). Conclusion The neuroprotective effects of OLE on heroininduced brain damage are associated with its properties of antioxidant and inhibiting apoptosis.
油橄榄叶提取物 / 海洛因 / 海马 / 学习记忆 / 氧化损伤 / 免疫组织化学 / 小鼠
olive leaves extract / heroin / hippocampus / learning and memory / oxidative damage / apoptosis / immunohistochemistry
［1］Li QQ, Sun ChY, Luo YX, et al. A conjugate vaccine attenuates morphine- and heroin-induced behavior in rats ［J］. Int J Neuropsychopharmacol, 2015, 18(5): 1-11.
［2］Bogen IL, Boix F, Nerem E, et al. A monoclonal antibody specific for 6-monoacetylmorphine reduces acute heroin effects in mice ［J］. J Pharmacol Exp Ther, 2014, 349(3): 568576.
［3］Feng HL, Li ChY, Yu ShY, et al. Effects of heroin on SOD and CAT activity and MDA content and histological structure in the lungs of the filial mice and mother mice［J］. Acta Anatomica Sinica, 2009, 40(2):288-294. (in Chinese)
冯红丽, 李重阳, 俞诗源,等. 海洛因对仔鼠和母鼠肺中SOD、CAT活力和MDA含量及组织结构的影响［J］. 解剖学报, 2009, 40(2): 288-294.
［4］Yuan J, Liu Y, Wang YK, et al. Reduced striatal dopamine transporter levels in chronic heroin dependent subjects and METH dependent subjects: A99mTc-TRODAT-1 SPECT imaging study ［J］. J Nucl Med, 2013, 54(2): 1852-1858.
［5］Schmidt A, Walter M, Gerber H, et al. Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity［J］. Brain, 2015, 138(1): 217-228.
［6］Kaeidi A, Esmaeili-Mahani S, Sheibani V, et al. Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies［J］. J Ethnopharmacol, 2011, 136(1):188-196.
［7］Turkez H, Togar B, Polat E. Olive leaf extract modulates permethrin induced genetic and oxidative damage in rats［J］. Cytotechnology, 2012, 64(4):459-464.
［8］Wang Y, Wang ShQ, Cui WH, et al. Olive leaf extract inhibits lead poisoning-induced brain injury［J］. Neural regeneration research, 2013, 8(22): 2021-2029.
［9］Park PE, Vendruscolo LF, Schlosburg JE, et al. Corticotropin-releasing factor (CRF) and α2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats［J］. Int J Neuropsychopharmacol, 2013, 16(8): 1867-1875.
［10］Su D, Zhao Y, Xu H, et al. Isoflurane exposure during mid-adulthood attenuates age-related spatial memory impairment in APP/PS1 transgenic mice［J］. PLoS One, 2012, 7(11):150-172.
［11］Ma XR, Sun ZK, Liu YR, et al. Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia［J］. Neural Regen Res, 2013, 8(22):2050-2059.
［12］Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates［M］. Sydney: Academic Press, 2005, 12-92.
［13］Jiang LH, Luo X, He W, et al. Effects of exogenous hydrogen sulfide on apoptosis proteins and oxidative stress in the hippocampus of rats undergoing heroin withdrawal［J］.Arch Pharm Res, 2011, 34(12): 2155-2162.
［14］Wang Y, Li ChY, Yu ShY, et al. Effects on the structure of cerebral lobe cortex temporal and capabiliby of learning and memory of filial mice after administration of heroin and ephedrine［J］. Acta Anatomica Sinica, 2009, 40 (5):724-31.(in Chinese)
王昱, 李重阳, 俞诗源,等. 注射海洛因、麻黄素对仔鼠大脑颞叶皮层结构及学习记忆能力的影响［J］.解剖学报, 2009, 40 (5):724-731.
［15］Eslami H, Sharifi AM. Role of Bax protein and Caspase-3 at high glucose-induced apoptosis in human embryonic kidney (HEK) 293 cells［J］. Zahedan Journal of Research in Medical Sciences, 2013, 15(5): 25-29.
甘肃省自然科学基金项目;甘肃省高等学校科研项目
/
| 〈 |
|
〉 |
