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6-OHDA 对帕金森病大鼠模型高碳酸血症通气反应的影响。

Effect of 6-OHDA on hypercapnic ventilatory response in the rat model of Parkinson's disease.

机构信息

Department of Respiration Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

出版信息

Physiol Res. 2019 Apr 30;68(2):285-293. doi: 10.33549/physiolres.933949. Epub 2019 Jan 10.

Abstract

Breathing impairments, such as an alteration in breathing pattern, dyspnoea, and sleep apnoea, are common health deficits recognised in Parkinson's disease (PD). The mechanism that underlies these disturbances, however, remains unclear. We investigated the effect of the unilateral damage to the rat nigrostriatal pathway on the central ventilatory response to hypercapnia, evoked by administering 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). The respiratory experiments were carried out in conscious animals in the plethysmography chamber. The ventilatory parameters were studied in normocapnic and hyperoxic hypercapnia before and 14 days after the neurotoxin injection. Lesion with the 6-OHDA produced an increased tidal volume during normoxia. The magnified response of tidal volume and a decrease of breathing frequency to hypercapnia were observed in comparison to the pre-lesion and sham controls. Changes in both respiratory parameters resulted in an increase of minute ventilation of the response to CO(2) by 28% in comparison to the pre-lesion state at 60 s. Our results demonstrate that rats with implemented unilateral PD model presented an altered respiratory pattern most often during a ventilatory response to hypercapnia. Preserved noradrenaline and specific changes in dopamine and serotonin characteristic for this model could be responsible for the pattern of breathing observed during hypercapnia.

摘要

呼吸障碍,如呼吸模式改变、呼吸困难和睡眠呼吸暂停,是帕金森病(PD)中常见的健康缺陷。然而,这些紊乱的潜在机制仍不清楚。我们研究了单侧破坏大鼠黑质纹状体通路对 6-羟多巴胺(6-OHDA)注入右侧内侧前脑束(MFB)诱发的中枢性通气反应的影响。呼吸实验在清醒动物的 plethysmography 室中进行。在神经毒素注射前和 14 天后,在常氧和高氧高碳酸血症下研究通气参数。6-OHDA 损伤导致正常氧合时潮气量增加。与损伤前和假对照相比,观察到潮气量和呼吸频率对高碳酸血症的放大反应增加。两种呼吸参数的变化导致每分钟通气量增加 28%,以响应 CO2 比损伤前状态在 60 秒时增加。我们的结果表明,实施单侧 PD 模型的大鼠在高碳酸血症通气反应中表现出改变的呼吸模式。保留的去甲肾上腺素和这种模型特有的多巴胺和 5-羟色胺的特定变化可能是导致高碳酸血症期间观察到的呼吸模式的原因。

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