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菠萝蛋白酶对帕金森病大鼠模型内侧隔核 6-OHDA 注射后运动反应的影响。

Effects of bromelain on motor responses following intra-medial forebrain bundle 6-OHDA injection in rat model of parkinsonism.

机构信息

Discipline of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa.

出版信息

Metab Brain Dis. 2019 Dec;34(6):1557-1564. doi: 10.1007/s11011-019-00462-9. Epub 2019 Jul 22.

DOI:10.1007/s11011-019-00462-9
PMID:31332728
Abstract

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. The conventional therapeutic measures which include the widely used L-DOPA therapy, are inefficient especially when dopamine loss is severe, and the physical symptoms are full blown. Since neuroinflammation is a core feature of PD, this raised the question of whether early treatment with an anti-inflammatory agent may provide a more efficient intervention for PD. In this study, we investigated the effect of bromelain (an anti-inflammatory drug) on motor responses and dopamine levels in a parkinsonian rat model. Male Sprague-Dawley rats were lesioned stereotaxically with the neurotoxin 6-OHDA. The anti-inflammatory agent, bromelain (40 mg/kg i.p) was used to treat a subset of the rats prior to or 24 h post 6-OHDA lesion. Locomotor activity was assessed after 6-OHDA injection, using the cylinder and step tests. The cortical and striatal concentrations of dopamine were also measured. 6-OHDA injection resulted in marked motor impairment which was prevented by pretreatment with bromelain prior to the lesion. Also, the injection of 6-OHDA into the medial forebrain bundle resulted in a significant reduction in dopamine concentration in the striatum and PFC. Bromelain treatment did not alter the suppression of cortical and striatal dopamine levels. Pre-treatment with bromelain reduced the motor dysfunction in the parkinsonian rat model of PD. The efficacy of treatment with bromelain does not appear to be via preservation of the dopaminergic system. The efficacy of bromelain in 6-OHDA injected rats still remains unclear.

摘要

帕金森病(PD)的特征是黑质致密部多巴胺能神经元进行性丧失。包括广泛使用的 L-DOPA 疗法在内的传统治疗措施在多巴胺丢失严重且身体症状完全爆发时效率低下。由于神经炎症是 PD 的核心特征,这就提出了一个问题,即早期使用抗炎药是否可能为 PD 提供更有效的干预。在这项研究中,我们研究了菠萝蛋白酶(一种抗炎药物)对帕金森病大鼠模型运动反应和多巴胺水平的影响。雄性 Sprague-Dawley 大鼠通过立体定向注射神经毒素 6-OHDA 进行损伤。抗炎药菠萝蛋白酶(40mg/kg,ip)用于在 6-OHDA 损伤前或损伤后 24 小时治疗一部分大鼠。在 6-OHDA 注射后,使用圆筒和台阶测试评估运动活性。还测量了皮质和纹状体中的多巴胺浓度。6-OHDA 注射导致明显的运动障碍,而在损伤前用菠萝蛋白酶预处理可预防。此外,6-OHDA 注射到中脑束导致纹状体和 PFC 中的多巴胺浓度显著降低。菠萝蛋白酶处理不会改变皮质和纹状体多巴胺水平的抑制。预处理用菠萝蛋白酶可减少 PD 帕金森病大鼠模型的运动功能障碍。菠萝蛋白酶治疗的疗效似乎不是通过多巴胺能系统的保护来实现的。在 6-OHDA 注射大鼠中,菠萝蛋白酶的疗效仍然不清楚。

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