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过氧化物酶体增殖物激活受体γ不会改变肝硬化大鼠模型中CA1锥体神经元的电生理特性改变。

Peroxisome proliferator-activated receptor-γ doesn't modify altered electrophysiological properties of the CA1 pyramidal neurons in a rat model of hepatic cirrhosis.

作者信息

Tahamtan Mahshid, Aghaei Iraj, Shabani Mohammad, Nazari Abbas, Pooladvand Vahid, Razavinasab Moazamehosadat

机构信息

Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.

Neuroscience Research Center, Guilan University of Medical Sciences, Rasht, Iran.

出版信息

Metab Brain Dis. 2022 Dec;37(8):2687-2697. doi: 10.1007/s11011-022-01057-7. Epub 2022 Aug 9.

Abstract

Regarding the low quality of life due to the cognitive complications in the patients with hepatic cirrhosis (HC), the goal of this study was to examine the possible neuroprotective effect of pioglitazone (PIO) on the electrophysiological alterations of hippocampus, a major area of cognition, in the experimental model of bile duct ligation (BDL). We used adult male Wistar rats in the present study to perform BDL or sham surgery. Pioglitazone was administered in BDL rats two weeks after the surgery for the next continuous four weeks. The effects of pioglitazone on BDL-induced electrophysiological alterations of the CA1 pyramidal neurons in the hippocampus were evaluated by whole-cell patch clamp recordings. Our findings demonstrated that chronic administration of PIO could not reverse the electrophysiological changes in the CA1 pyramidal neurons of the hippocampus in BDL rats but could improve the hepatic dysfunction.Together, the results of this study suggest that PIO administration cannot counteract altered intrinsic properties of the hippocampal neurons which has been shown recently as an involved mechanism of the cognitive impairments in hepatic encephalopathy (HE).

摘要

鉴于肝硬化(HC)患者因认知并发症导致生活质量低下,本研究的目的是在胆管结扎(BDL)实验模型中,研究吡格列酮(PIO)对认知的主要区域海马体电生理改变可能具有的神经保护作用。在本研究中,我们使用成年雄性Wistar大鼠进行BDL手术或假手术。术后两周开始对BDL大鼠连续四周给予吡格列酮。通过全细胞膜片钳记录评估吡格列酮对BDL诱导的海马体CA1锥体神经元电生理改变的影响。我们的研究结果表明,长期给予PIO不能逆转BDL大鼠海马体CA1锥体神经元的电生理变化,但可改善肝功能障碍。总之,本研究结果表明,给予PIO不能抵消海马神经元内在特性的改变,而这种改变最近已被证明是肝性脑病(HE)认知障碍的一种相关机制。

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