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长期摄入乙醇会诱导大鼠肾脏中肾小球滤过屏障蛋白基因表达改变,并增加基质金属蛋白酶的活性。

Chronic ethanol ingestion induces glomerular filtration barrier proteins genes expression alteration and increases matrix metalloproteinases activity in the kidney of rats.

作者信息

Samadi Mahrokh, Shirpoor Alireza, Afshari Ali Taghizadeh, Kheradmand Fatemeh, Rasmi Yousef, Sadeghzadeh Maryam

机构信息

Faculty of Medicine, Department of Physiology, Urmia University of Medical Sciences, Urmia, Iran.

Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

Interv Med Appl Sci. 2018 Sep;10(3):171-177. doi: 10.1556/1646.10.2018.23.

Abstract

BACKGROUND

Chronic alcohol ingestion-induced kidney structure and function alterations are very well known, but the precise underlying molecular mediators involved in ethanol-induced kidney abnormalities remain elusive. The aim of this study was to investigate the effect of chronic ethanol exposure on matrix metalloproteinase 2, 9 (MMP), glomerular filtration barrier proteins (nephrin and podocin), as well as vascular endothelial growth factor receptor 1, 2 (VEGFRs) isoforms gene expression in the kidney of rats.

METHODS

Sixteen male Wistar rats with an initial body weight of 220 ± 10 g were divided into the following two groups: (1) control and (2) ethanol (4.5 g/kg BW).

RESULTS

After 6 weeks of treatment, the results revealed a significant increase in isoforms VEGFR1 and VEGFR2 of VEGFR gene expression, significant increases of MMP2 and MMP9 activities, as well as significant decrease of nephrin and podocin gene expressions in the ethanol group, compared with that in the control group.

CONCLUSION

These findings indicate that ethanol-induced kidney abnormalities may be in part associated with alteration in expressions of VEGFRs, nephrin, and podocin and in increasing activities of MMP2 and MMP9 as key molecular mediators in the kidney function.

摘要

背景

长期饮酒导致的肾脏结构和功能改变已广为人知,但乙醇诱导肾脏异常的确切潜在分子介质仍不清楚。本研究的目的是探讨长期乙醇暴露对大鼠肾脏基质金属蛋白酶2、9(MMP)、肾小球滤过屏障蛋白(nephrin和podocin)以及血管内皮生长因子受体1、2(VEGFRs)亚型基因表达的影响。

方法

将16只初始体重为220±10 g的雄性Wistar大鼠分为以下两组:(1)对照组和(2)乙醇组(4.5 g/kg体重)。

结果

治疗6周后,结果显示,与对照组相比,乙醇组VEGFR基因表达的VEGFR1和VEGFR2亚型显著增加,MMP2和MMP9活性显著增加,nephrin和podocin基因表达显著降低。

结论

这些发现表明,乙醇诱导的肾脏异常可能部分与VEGFRs、nephrin和podocin表达的改变以及MMP2和MMP9活性增加有关,这些是肾脏功能中的关键分子介质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e7/6343583/981a58692f7a/imas-10-03-23_f001.jpg

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