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肝性脑病可诱导大鼠大脑中NMDA受体GluN1亚基基因表达的位点特异性变化。

Hepatic encephalopathy induces site-specific changes in gene expression of GluN1 subunit of NMDA receptor in rat brain.

作者信息

Ahmadi Shamseddin, Poureidi Mahsa, Rostamzadeh Jalal

机构信息

Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, P.O. Box 416, Sanandaj, Iran,

出版信息

Metab Brain Dis. 2015 Aug;30(4):1035-41. doi: 10.1007/s11011-015-9669-x. Epub 2015 Apr 22.

DOI:10.1007/s11011-015-9669-x
PMID:25896221
Abstract

We investigate changes in gene expression of GluN1 subunit of N-Methyl-D-Aspartate (NMDA) receptor in the prefrontal cortex (PFC), hippocampus and striatum in a rat model of hepatic encephalopathy (HE). We used male Wistar rats in which HE was induced after a common bile duct ligation (BDL). The animals were divided into three sets, and each set included three groups of control, sham operated and BDL. In the first set of animals, blood samples collected for biochemical analysis on day 21 of BDL. In the second set, changes in nociception threshold was assessed on day 21 of BDL using a hotplate test. In the third set, whole brain extracted, and the PFC, the hippocampus and the striatum in each rat were immediately dissected. We used a semi-quantitative RT-PCR method for evaluating the GluN1 gene expression. The biochemical analyses showed that plasma levels of ammonia and bilirubin in BDL rats were significantly increased compared to the sham control group on day 21 of BDL (P < 0.01). Nociception threshold was also increased in rats with BDL compared to sham group (P < 0.001). The results revealed that the GluN1 gene expression at mRNA levels in BDL group was decreased by 19 % in the PFC (P < 0.05) but increased by 82 % in the hippocampus (P < 0.01) compared to the sham control group; however, no significant change was observed in the striatum. It can be concluded that HE affects the GluN1 gene expression in rat brain with a site-specific pattern, and the PFC and hippocampus are more sensitive areas than striatum.

摘要

我们研究了肝性脑病(HE)大鼠模型前额叶皮质(PFC)、海马体和纹状体中N-甲基-D-天冬氨酸(NMDA)受体GluN1亚基的基因表达变化。我们使用雄性Wistar大鼠,通过胆总管结扎(BDL)诱导其发生HE。将动物分为三组,每组包括对照组、假手术组和BDL组。在第一组动物中,于BDL后第21天采集血样进行生化分析。在第二组中,于BDL后第21天使用热板试验评估痛觉阈值变化。在第三组中,取出全脑,立即解剖每只大鼠的PFC、海马体和纹状体。我们使用半定量RT-PCR方法评估GluN1基因表达。生化分析表明,在BDL后第21天,BDL大鼠的血浆氨和胆红素水平与假手术对照组相比显著升高(P < 0.01)。与假手术组相比,BDL大鼠的痛觉阈值也升高(P < 0.001)。结果显示,与假手术对照组相比,BDL组PFC中GluN1基因的mRNA水平表达下降了19%(P < 0.05),而海马体中升高了82%(P < 0.01);然而,纹状体中未观察到显著变化。可以得出结论,HE以位点特异性模式影响大鼠脑内GluN1基因表达,且PFC和海马体比纹状体更敏感。

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