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依达拉奉减轻喹啉酸诱导的类似亨廷顿病症状:雄性 Wistar 大鼠神经行为、生化和组织学方法的初步研究

Quinolinic Acid-Induced Huntington Disease-Like Symptoms Mitigated by Potent Free Radical Scavenger Edaravone-a Pilot Study on Neurobehavioral, Biochemical, and Histological Approach in Male Wistar Rats.

机构信息

Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, 600 113, India.

出版信息

J Mol Neurosci. 2018 Nov;66(3):322-341. doi: 10.1007/s12031-018-1168-1. Epub 2018 Oct 3.

Abstract

In this study, we demonstrated for the first time the neuroprotective role of edaravone (Eda) (5 and 10 mg/kg b.w.), a potent free radical scavenger against the unilateral stereotaxic induction of quinolinic acid (QA) (300 nm/4 μl saline)-induced Huntington disease (HD)-like symptoms in behavioral, biochemical, and histological features in male Wistar rats striatum. QA induction, which mimics the early stage of HD, commonly causes oxidative stress to the cell and decreases the antioxidant defense mechanism by altering the level of lipid peroxidation (LPO), protein carbonyls, and nitrate concentration (NO) and the activities of glutathione family enzymes (GPx, GST, GR) and acetyl choline esterase concentration (AChE) which was found to be ameliorated by Eda treatment in both the tested doses 5 and 10 mg/kg b.w. in the significance of P < 0.05 and P < 0.01, respectively. Finally histopathological analysis by hematoxylin and eosin stain concluded the promising neurodefensive role of Eda in rat striatum at the dosage of 10 mg/kg b.w., with the decreased tissue damage and the number of damaged granular cells when compared to QA-induced groups.

摘要

在这项研究中,我们首次证明了依达拉奉(Eda)(5 和 10mg/kg bw)的神经保护作用,它是一种有效的自由基清除剂,可对抗单侧立体定向诱导的喹啉酸(QA)(300nm/4μl 生理盐水)诱导的亨廷顿病(HD)样症状,表现在雄性 Wistar 大鼠纹状体的行为、生化和组织学特征上。QA 诱导模拟了 HD 的早期阶段,通常会导致细胞氧化应激,并通过改变脂质过氧化(LPO)、蛋白羰基和硝酸盐浓度(NO)以及谷胱甘肽家族酶(GPx、GST、GR)的活性来改变抗氧化防御机制,乙酰胆碱酯酶浓度(AChE),发现 Eda 治疗在 5 和 10mg/kg bw 两种测试剂量下均可改善这些变化,分别具有统计学意义(P<0.05 和 P<0.01)。最后,通过苏木精和伊红染色的组织病理学分析得出,Eda 在 10mg/kg bw 的剂量下对大鼠纹状体具有有前景的神经保护作用,与 QA 诱导组相比,组织损伤和受损颗粒细胞的数量减少。

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