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Salusin-α和Salusin-β对肾脏缺血/再灌注损伤的保护作用及其在缺血性急性肾衰竭中的水平

Protective effects of salusin-α and salusin-β on renal ischemia/reperfusion damage and their levels in ischemic acute renal failure.

作者信息

Cakir M, Duzova H, Taslidere A, Orhan G, Ozyalin F

机构信息

a Departments of Physiology.

b Histology and Embryology.

出版信息

Biotech Histochem. 2017;92(2):122-133. doi: 10.1080/10520295.2017.1283056. Epub 2017 Mar 6.

DOI:10.1080/10520295.2017.1283056
PMID:28296550
Abstract

Salusin-α and salusin-β are expressed in many tissues including the central nervous system, vessels and kidneys; they have been shown to decrease endoplasmic reticulum stress during heart ischemia/reperfusion (I/R) and to decrease apoptosis. We investigated the relation of salusin-α and salusin-β levels to acute ischemic renal failure. We also investigated whether these peptides are protective against renal I/R damage. Fifty-three rats were divided into six groups: control, I/R, I/R + salusin-α1, I/R + salusin-α10, I/R + salusin-β1 and I/R + salusin-β10. After removing the right kidney, the left kidney was subjected to ischemia for 1 h and reperfusion for 23 h. The treatment groups were injected subcutaneously at the beginning of ischemia with 1 or 10 μg/kg salusin-α, and 1 or 10 μg/kg salusin-β. Histopathology was assessed at the end of the experiment. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) activity and malondialdehyde (MDA) levels were measured in the kidney tissue. Serum levels of blood urea nitrogen (BUN), creatinine (Cre), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) also were measured. Levels of salusin-α and salusin-β were measured in the serum and kidney tissues of the control and I/R groups. SOD, CAT and GSH-PX activities were decreased and the levels of MDA, TNF-α, IL-6, IL-1β, BUN and Cre were increased in the I/R group compared to controls. Severe glomerular and tubular damage was apparent in the I/R group compared to controls. The level of salusin-β was decreased in the serum and kidney tissue of the I/R group compared to controls, whereas the level of salusin-α was decreased in the serum and increased in the kidney tissue. Salusin-α and salusin-β administration increased SOD and GSH-PX enzyme activation and decreased the levels of MDA, TNF-α, IL-6 and IL-1β compared to the I/R group. BUN and Cre levels were decreased in the I/R + salusin-α1 group and the level of Cre was decreased in I/R + salusin-β10 group compared to the I/R group. We demonstrated a protective effect of salusin-α and salusin-β against renal I/R damage. Changes in the levels of salusin-α and salusin-β in the I/R group suggest that these peptides may be associated with acute renal failure.

摘要

Salusin-α和Salusin-β在包括中枢神经系统、血管和肾脏在内的许多组织中均有表达;研究表明,它们可减轻心脏缺血/再灌注(I/R)期间的内质网应激,并减少细胞凋亡。我们研究了Salusin-α和Salusin-β水平与急性缺血性肾衰竭的关系。我们还研究了这些肽是否对肾脏I/R损伤具有保护作用。53只大鼠被分为六组:对照组、I/R组、I/R + Salusin-α1组、I/R + Salusin-α10组、I/R + Salusin-β1组和I/R + Salusin-β10组。切除右肾后,左肾进行1小时缺血和23小时再灌注。治疗组在缺血开始时皮下注射1或10μg/kg的Salusin-α以及1或10μg/kg的Salusin-β。实验结束时进行组织病理学评估。检测肾组织中的超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-PX)活性以及丙二醛(MDA)水平。还检测血清中的血尿素氮(BUN)、肌酐(Cre)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)水平。检测对照组和I/R组血清及肾组织中的Salusin-α和Salusin-β水平。与对照组相比,I/R组的SOD、CAT和GSH-PX活性降低,而MDA、TNF-α、IL-6、IL-1β、BUN和Cre水平升高。与对照组相比,I/R组出现明显的严重肾小球和肾小管损伤。与对照组相比,I/R组血清和肾组织中的Salusin-β水平降低,而Salusin-α在血清中降低但在肾组织中升高。与I/R组相比(给予)Salusin-α和Salusin-β可增加SOD和GSH-PX酶的活性,并降低MDA、TNF-α、IL-6和IL-1β的水平。与I/R组相比,I/R + Salusin-α1组的BUN和Cre水平降低,I/R + Salusin-β10组的Cre水平降低。我们证明了Salusin-α和Salusin-β对肾脏I/R损伤具有保护作用。I/R组中Salusin-α和Salusin-β水平的变化表明这些肽可能与急性肾衰竭有关。

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