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肌肽对 6-羟多巴胺诱导的偏侧帕金森病大鼠具有神经保护作用。

Carnosine exerts neuroprotective effect against 6-hydroxydopamine toxicity in hemiparkinsonian rat.

机构信息

Neurophysiology Research Center, Shahed University, Tehran, Iran.

出版信息

Mol Neurobiol. 2015;51(3):1064-70. doi: 10.1007/s12035-014-8771-0. Epub 2014 Jun 18.

Abstract

Parkinson's disease (PD) is the second most common disorder of the central nervous system due to the degeneration of mesencephalic dopaminergic neurons. Current treatments for PD have a symptomatic relief strategy with no prevention of disease progression. Due to the neuroprotective and antiapoptotic potential of the natural dipeptide carnosine, this study was conducted to assess its beneficial effect in 6-hydroxydopamine (6-OHDA)-induced model of PD in rat. Unilateral intrastriatal 6-OHDA-lesioned rats received i.p. carnosine at a dose of 250 mg/kg twice at an interval of 24 h, which started presurgery. Apomorphine caused contralateral rotations, a significant reduction in the number of Nissl-stained neurons on the left side of the substantia nigra, and increased apoptosis was observed with enhanced oxidative stress burden in 6-OHDA-lesioned rats. Carnosine pretreatment significantly reduced rotations, attenuated apoptosis, and restored malondialdehyde and nitrite content and catalase activity with no significant effect on reduced glutathione (GSH). These results indicate that prelesion administration of carnosine could exert neuroprotection against 6-OHDA toxicity, and this may be of benefit in patients with early PD.

摘要

帕金森病(PD)是由于中脑多巴胺能神经元退化导致的第二大常见中枢神经系统疾病。目前 PD 的治疗方法具有对症缓解策略,无法预防疾病进展。由于天然二肽肌肽具有神经保护和抗细胞凋亡作用,因此进行了这项研究,以评估其在大鼠 6-羟多巴胺(6-OHDA)诱导的 PD 模型中的有益作用。单侧纹状体 6-OHDA 损伤大鼠腹腔内给予 250mg/kg 肌肽,两次间隔 24 小时,于术前开始给药。阿扑吗啡引起对侧旋转,黑质左侧尼氏染色神经元数量显著减少,6-OHDA 损伤大鼠的氧化应激负担增加,凋亡增加。肌肽预处理可显著减少旋转,减轻凋亡,并恢复丙二醛和亚硝酸盐含量以及过氧化氢酶活性,对还原型谷胱甘肽(GSH)无显著影响。这些结果表明,肌肽的损伤前给药可发挥神经保护作用,对抗 6-OHDA 毒性,这可能对早期 PD 患者有益。

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