Abstract：
Oxidative stress from generation of increased reactive oxygen species or has been reported to play an important role in dementia. Oxidative stress due to free radicals of oxygen or reactive oxygen species could be precipitating factors in the etiology of dementia. Apomorphine has been reported to have neuroprotective effects. To monitor memory enhancing and neuroprotective effects of apomorphine, we determined the antioxidant enzymes activities, lipid peroxidation, acetylcholine esterase (AChE) activity in brain and plasma, following repetitive administration of apomorphine in rat model of dementia. Biogenic amine levels were also monitored in hippocampus. Repeated administration of scopolamine was taken as an animal model of dementia. Decreased glutathione peroxidase, superoxide dismutase and catalase activities were observed in these animal models of dementia. While increased lipid peroxidation was also observed in the brain and plasma samples. The results showed significant effects of apomorphine. The activities of antioxidant enzymes displayed increased activities in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly higher in brain and plasma of apomorphine treated rats. Superoxide dismutase (SOD) was significantly decreased in plasma of scopolamine injected rats; and a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in scopolamine treated rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM). Short-term memory and long-term memory was impaired significantly in scopolamine treated rats, which was prevented by apomorphine. Moreover, a marked decrease in biogenic amines was also found in the brain of scopolamine treated rats and was reverted in apomorphine treated rats. Results showed that scopolamine-treatment induced memory impairment and induced oxidative stress in rats as compared to saline-treated controls. These impairments were significantly restored by apomorphine administration. In conclusion, our data suggests that apomorphine at the dose of 1 mg/kg could be a potential therapeutic agent to treat dementia and related disorders.
摘要：
来自产生增加的活性氧的氧化应激或已被报道在痴呆中起重要作用。氧自由基或活性氧引起的氧化应激可能是痴呆病因的诱发因素。据报道，阿扑吗啡具有神经保护作用。为了监测阿扑吗啡的记忆增强和神经保护作用，我们确定了抗氧化酶的活性，脂质过氧化，脑和血浆中的乙酰胆碱酯酶（AChE）活性，阿朴吗啡在痴呆大鼠模型中重复给药。还监测海马中的生物胺水平。重复给药东莨菪碱作为痴呆的动物模型。谷胱甘肽过氧化物酶减少,在这些痴呆动物模型中观察到超氧化物歧化酶和过氧化氢酶活性。虽然在脑和血浆样品中也观察到脂质过氧化增加。结果表明，阿朴吗啡的作用明显。抗氧化酶的活性在脑和血浆中均显示出增加的活性。发现阿扑吗啡治疗的大鼠的脑和血浆中的谷胱甘肽过氧化物酶和过氧化氢酶活性明显更高。注射东pol碱的大鼠血浆中超氧化物歧化酶（SOD）显着降低；并且还观察到脑中SOD的降低趋势（无显着）。东pol碱治疗的大鼠脑和血浆中的AChE活性显着降低。通过Morris水迷宫（MWM）评估本研究中大鼠的学习和记忆。东pol碱治疗的大鼠的短期记忆和长期记忆明显受损，阿扑吗啡阻止了这种情况。此外，在东pol碱治疗的大鼠的大脑中也发现了生物胺的显着减少，并且在阿扑吗啡治疗的大鼠中有所恢复。结果表明，与生理盐水治疗的对照组相比，东莨菪碱治疗可引起大鼠记忆障碍和氧化应激。通过阿朴吗啡给药，这些损伤得到了显着恢复。总之,我们的数据表明,剂量为1mg/kg的阿朴吗啡可能是治疗痴呆和相关疾病的潜在治疗剂.
