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GABA-B受体调节在大鼠MPTP诱导的帕金森病中的可能作用。

Possible role of GABA-B receptor modulation in MPTP induced Parkinson's disease in rats.

作者信息

Tyagi Ravi Kant, Bisht Rohit, Pant Jatin, Kumar Puneet, Majeed Abu Bakar Abdul, Prakash Atish

机构信息

Department of Pharmacology, Indo Soviet Friendship (ISF) College of Pharmacy, Moga 142001, Punjab, India.

Faculty of Pharmacy, Campus Puncak Alam, Universiti Teknologi MARA (UiTM), 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

出版信息

Exp Toxicol Pathol. 2015 Feb;67(2):211-7. doi: 10.1016/j.etp.2014.12.001. Epub 2014 Dec 26.

Abstract

Accumulating evidence strongly suggests that gamma amino butyric acid (GABA) receptors play a crucial role in the pathogenesis of Parkinson's disease (PD). Therefore, the present study was designed to investigate the role of GABA-B receptor modulation in experimental models of MPTP-induced PD. MPTP was administered repeatedly on 1st, 7th and 14th day intranigrally for the induction of PD in Male Wistar rats. Baclofen (10 and 20mg/kg) and GABA-B antagonist CGP35348 (10mg/kg) were given after induction of PD for 14 days. Different behavioural tasks were performed during 1st, 14th, 21st, 28th days after MPTP injection and biochemical parameters were estimated on day 28th. Central administration of MPTP showed significant impairment of motor behaviour and marked increase of oxidative damage LPO and GSH in striatum and cortex. Pro-inflammatory cytokines like TNF-α and IL-β were significantly increased in striatum region of MPTP treated rats. However, post treatment with baclofen significantly improved the motor abnormalities and attenuated the oxidative damage and neuro-inflammation in MPTP treated rats. CGP35348, GABA-B receptor antagonist, reversed the protective effect of baclofen GABA-B receptor play role in the neuroprotection. The present study concluded that baclofen produce beneficial effect against MPTP induced PD like symptoms rats through GABAergic mechanism.

摘要

越来越多的证据有力地表明,γ-氨基丁酸(GABA)受体在帕金森病(PD)的发病机制中起关键作用。因此,本研究旨在探讨GABA-B受体调节在MPTP诱导的PD实验模型中的作用。在雄性Wistar大鼠的黑质内于第1、7和14天重复给予MPTP以诱导PD。在诱导PD 14天后给予巴氯芬(10和20mg/kg)和GABA-B拮抗剂CGP35348(10mg/kg)。在注射MPTP后的第1、14、21、28天进行不同的行为任务,并在第28天评估生化参数。MPTP的中枢给药显示运动行为明显受损,纹状体和皮质中的氧化损伤LPO和GSH显著增加。MPTP处理的大鼠纹状体区域中促炎细胞因子如TNF-α和IL-β显著增加。然而,巴氯芬治疗后显著改善了MPTP处理大鼠的运动异常,并减轻了氧化损伤和神经炎症。GABA-B受体拮抗剂CGP35348逆转了巴氯芬的保护作用,GABA-B受体在神经保护中起作用。本研究得出结论,巴氯芬通过GABA能机制对MPTP诱导的大鼠PD样症状产生有益作用。

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