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缺血再灌注后小鼠肝脏中AQP基因表达的研究。

Investigate of AQP gene expression in the liver of mice after ischemia-reperfusion.

作者信息

Karimi Solmaz, Khatami Saeid Reza, Azarpira Negar, Galehdari Hamid, Pakbaz Sara

机构信息

Department of Genetics, Faculty of Science, Shahid Chamran University, Ahvaz, Iran.

Transplant Research Center, Shiraz Institute for Stem Cell and Regenerative Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Mol Biol Rep. 2018 Dec;45(6):1769-1774. doi: 10.1007/s11033-018-4320-7. Epub 2018 Aug 24.

Abstract

Ischemia-reperfusion (IR) injury usually occurs during liver transplantation. Aquaporins (AQPs) are transmembrane channels that facilitate water permeability through cell membranes and are essential for the regulation of water homeostasis. Changes in the AQPs expression have been correlated with several inflammatory diseases. Less is known about AQPs expression in hepatic ischemia reperfusion injury. To clarify the roles of AQPs in IR injury, in this current study we examined the gene expression patterns of AQP1, 8 and 9 in the liver after IR injury. Male balb/c mice were exposed to partial (70%) hepatic ischemia for 65 min and then randomized into five groups of reperfusion [0 h (A), 8 h (B), 1 day (C), 3 days (D), and 7 days (E)]. A surgical group was also selected as the sham group. Serum and liver tissue samples were collected for evaluation of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver histopathology. Real time PCR was performed to evaluate the AQPs expression. I/R injury resulted in a significant increase in ALT and AST (p < 0.05) compared to sham mice in each group. The gene expression of AQPs was significantly increased in the IR group compared with the sham group (p < 0.05). AQP8 and AQP1 after 8 h (group B) showed the highest gene expression in comparison with other groups, but the highest level of AQP9 gene expression was observed after 1 day (group C). Pathologic changes in the liver after reperfusion were confirmed the IR. In the IR group cytoplasmic vacuolization, inflammatory cell infiltration and focal necrosis were detected. In conclusion, our findings indicated that the damage caused by ischemia-reperfusion in the liver can change the expression of AQP genes, which can interfere with hepatocellular homeostasis and their function. Upregulation of AQP1, 8 and 9 could contribute to the development of hepatocellular swelling after hepatic IR injury.

摘要

缺血再灌注(IR)损伤通常发生在肝移植过程中。水通道蛋白(AQPs)是跨膜通道,可促进水透过细胞膜,对调节水平衡至关重要。AQPs表达的变化与多种炎症性疾病相关。关于AQPs在肝缺血再灌注损伤中的表达了解较少。为阐明AQPs在IR损伤中的作用,在本研究中,我们检测了IR损伤后肝脏中AQP1、8和9的基因表达模式。雄性balb/c小鼠接受部分(70%)肝脏缺血65分钟,然后随机分为五组进行再灌注[0小时(A)、8小时(B)、1天(C)、3天(D)和7天(E)]。还选择一个手术组作为假手术组。收集血清和肝组织样本以评估丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和肝脏组织病理学。进行实时PCR以评估AQPs的表达。与每组假手术小鼠相比,I/R损伤导致ALT和AST显著升高(p<0.05)。与假手术组相比,IR组中AQPs的基因表达显著增加(p<0.05)。与其他组相比,8小时后(B组)的AQP8和AQP1显示出最高的基因表达,但AQP9基因表达的最高水平在1天后(C组)观察到。再灌注后肝脏的病理变化证实了IR。在IR组中检测到细胞质空泡化、炎性细胞浸润和局灶性坏死。总之,我们的研究结果表明,肝脏缺血再灌注造成的损伤可改变AQP基因的表达,这可能会干扰肝细胞内环境稳定及其功能。AQP1、8和9的上调可能导致肝IR损伤后肝细胞肿胀的发展。

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