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促红细胞生成素改善肝硬化大鼠模型的运动和认知功能障碍。

Erythropoietin ameliorates the motor and cognitive function impairments in a rat model of hepatic cirrhosis.

作者信息

Aghaei Iraj, Nazeri Masoud, Shabani Mohammad, Mossavinasab Marziehsadat, Mirhosseini Fatemeh Khaleghi, Nayebpour Mohsen, Dalili Afshin

机构信息

Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Metab Brain Dis. 2015 Feb;30(1):197-204. doi: 10.1007/s11011-014-9600-x. Epub 2014 Aug 13.

Abstract

Hepatic encephalopathy (HE) is a serious consequence of hepatic cirrhosis (HC). Previous studies have demonstrated cognitive impairments in both clinical and animal experiments of HC. Some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of HC. In the current study, the possible effect of erythropoietin (ERY) as a potent neuroprotective agent on motor and cognitive impairments induced by HC has been studied. Male Wistar rats (180-200 g) underwent bile duct ligation (BDL) or sham surgery. Administration of ERY (5,000 IU/kg, i.p., daily for three days) was initiated 2 weeks after surgery and lasted for the next 28 days. Open field, rotarod, Morris water maze and passive avoidance learning was used to evaluate the motor and cognitive function of the animals. ANOVA and repeated measures ANOVA were used to analyze the data. p < 0.05 was considered statistically significant. BDL rats had an increased level of hepatic enzymes and bilirubin. Impairment of balance function by BDL was reversed by ERY. Spatial and passive avoidance learning impairments observed in BDL rats were also reversed by chronic administration of ERY. ERY can be offered as a potential neuroprotective agent in the treatment of patients with HC that manifest mental dysfunctions. Though further studies are needed to clarify the exact mechanisms, the neuroprotective properties of ERY against BDL impairments were demonstrated in the current study.

摘要

肝性脑病(HE)是肝硬化(HC)的严重后果。先前的研究已在HC的临床和动物实验中证实了认知障碍。一些潜在的治疗药物已被用于减轻HC动物模型中的认知症状。在本研究中,已对促红细胞生成素(ERY)作为一种有效的神经保护剂对HC诱导的运动和认知障碍的可能作用进行了研究。雄性Wistar大鼠(180 - 200克)接受胆管结扎(BDL)或假手术。术后2周开始给予ERY(5000 IU/kg,腹腔注射,每天一次,共三天),并持续接下来的28天。采用旷场实验、转棒实验、莫里斯水迷宫实验和被动回避学习实验来评估动物的运动和认知功能。使用方差分析(ANOVA)和重复测量方差分析来分析数据。p < 0.05被认为具有统计学意义。BDL大鼠的肝酶和胆红素水平升高。ERY可逆转BDL导致的平衡功能损害。长期给予ERY也可逆转BDL大鼠中观察到的空间和被动回避学习障碍。ERY可作为一种潜在的神经保护剂用于治疗出现精神功能障碍的HC患者。尽管需要进一步研究来阐明确切机制,但本研究证明了ERY对BDL损伤具有神经保护特性。

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