吡拉西坦和长春胺对氟哌啶醇诱导帕金森病大鼠模型的神经保护作用

A. Sheref, Yahya M. Naguib, Elsayed Abouelnour, H. Salem, Mohammed S. Hassan, H. Abdel-Razek
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引用次数: 4

摘要

为评价促智药物吡拉西坦和长春胺对帕金森病(PD)大鼠的神经保护作用,将40只成年雄性Wistar白化大鼠随机分为5组:对照组、氟哌啶醇诱导PD组、PD组分别口服吡拉西坦(300 mg/kg/d)、长春胺(20 mg/kg/d)或两者同时口服。4周后采用步进试验评估运动性能。通过y迷宫、强迫游泳和嗅觉偏好测试进行认知和行为评价。采集血样,测定血清葡萄糖、钙、肌酸磷酸激酶(CPK)和神经胶质细胞源性神经营养因子(GDNF)。之后,处死大鼠,解剖其大脑。分离左半球纹状体组织,匀浆检测多巴胺、丙二醛(MDA)、亚硝酸盐/硝酸盐、还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)、肿瘤坏死因子-α (TNF-α)、白细胞介素-1 β (IL-1ß)。右半球进行黑质组织病理学检查。结果:PD组大鼠出现运动迟缓、认知障碍、抑郁样行为、低血氧,血清钙、GDNF、纹状体多巴胺、GSH、GPx、SOD降低,血清葡萄糖、CPK升高,纹状体MDA、亚硝酸盐/硝酸盐、IL-1ß、TNF-α升高。与PD组相比,两种药物均改善了神经功能障碍和生化指标。病理组织学结果显示,PD组神经退行性变和神经炎症,治疗组有所改善。吡拉西坦的作用主要是抗炎,长春胺的作用主要是抗氧化。联合治疗可更有效地改善氟哌啶醇引起的病变。结论:吡拉西坦和长春胺对氟哌啶醇诱导的PD具有神经保护作用,且合用更强。关键字
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Neuroprotective Effect of Piracetam and Vincamine in a Rat Model of Haloperidol-induced Parkinson's Disease
To evaluate the neuroprotective effect of nootropic drugs, piracetam and vincamine, on Parkinsonʹs disease (PD) in rats, forty adult male Wistar albino rats were randomized into five equal groups: control, haloperidol-induced PD group, and PD groups orally given piracetam (300 mg/kg/day), vincamine (20 mg/kg/day) or both. Four weeks later, motor performance was assessed by stepping test. Y-maze, forced swimming and olfactory preference tests were done for cognitive and behavioral evaluation. Blood samples were collected for measuring serum glucose, calcium, creatine phosphokinase (CPK) and glial cell-derived neurotrophic factor (GDNF). Thereafter, rats were sacrificed and brains were dissected. Striatal tissue of left hemisphere was isolated and homogenized for assay of dopamine, malondialdehyde (MDA), nitrite/nitrate, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß). Right hemisphere was used for histopathological examination of substantia nigra. Results: Rats of PD group showed bradykinesia, cognitive impairment, depressive-like behavior and hyposmia, reductions in serum calcium and GDNF, and in striatal dopamine, GSH, GPx and SOD, while serum glucose and CPK, and striatal MDA, nitrite/nitrate, IL-1ß and TNF-α were increased, as compared to control. Both drugs improved neurological dysfunction and biochemical parameters, as compared to PD group. The histopathological findings revealed neuro-degeneration and neuro-inflammation in PD group, that improved in treated groups. The piracetam effect was mainly anti-inflammatory, while vincamine was mainly antioxidant. Combined treatment resulted in a more potent amelioration of haloperidol-induced changes. Conclusion: Piracetam and vincamine exhibit neuroprotective activity in haloperidol-induced PD, that is more potent with their combination. Keywords
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