Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil.
Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil.
Biochim Biophys Acta Mol Basis Dis. 2018 Feb;1864(2):454-463. doi: 10.1016/j.bbadis.2017.10.027. Epub 2017 Oct 24.
During chronic limb ischemia, oxidative damage and inflammation are described. Besides oxidative damage, the decrease of tissue oxygen levels is followed by several adaptive responses. The purpose of this study was to determine whether supplementation with N-acetylcysteine (NAC) is effective in an animal model of chronic limb ischemia. Chronic limb ischemia was induced and animals were treated once a day for 30 consecutive days with NAC (30mg/kg). After this time clinical scores were recorded and soleus muscle was isolated and lactate levels, oxidative damage and inflammatory parameters were determined. In addition, several mechanisms associated with hypoxia adaptation were measured (vascular endothelial growth factor - VEGF and hypoxia inducible factor - HIF levels, ex vivo oxygen consumption, markers of autophagy/mitophagy, and mitochondrial biogenesis). The adaptation to chronic ischemia in this model included an increase in muscle VEGF and HIF levels, and NAC was able to decrease VEGF, but not HIF levels. In addition, ex vivo oxygen consumption under hypoxia was increased in muscle from ischemic animals, and NAC was able to decrease this parameter. This effect was not mediated by a direct effect of NAC on oxygen consumption. Ischemia was followed by a significant increase in muscle myeloperoxidase activity, as well as interleukin-6 and thiobarbituric acid reactive substances species levels. Supplementation with NAC was able to attenuate inflammatory and oxidative damage parameters, and improve clinical scores. In conclusion, NAC treatment decreases oxidative damage and inflammation, and modulates oxygen consumption under hypoxic conditions in a model of chronic limb ischemia.
在慢性肢体缺血中，会描述氧化损伤和炎症。除了氧化损伤外，组织氧水平的下降还会导致多种适应性反应。本研究的目的是确定 N-乙酰半胱氨酸 (NAC) 补充剂在慢性肢体缺血动物模型中的有效性。诱导慢性肢体缺血，动物每天接受 NAC（30mg/kg）治疗 30 天。经过这段时间后，记录临床评分，并分离比目鱼肌，测定乳酸水平、氧化损伤和炎症参数。此外，还测量了与缺氧适应相关的几种机制（血管内皮生长因子-VEGF 和缺氧诱导因子-HIF 水平、体外氧消耗、自噬/线粒体自噬标志物以及线粒体生物发生）。该模型中对慢性缺血的适应包括肌肉 VEGF 和 HIF 水平的增加，而 NAC 能够降低 VEGF，但不能降低 HIF 水平。此外，缺血动物肌肉在缺氧条件下的体外氧消耗增加，而 NAC 能够降低这一参数。这种作用不是 NAC 对氧消耗的直接作用介导的。缺血后肌肉髓过氧化物酶活性以及白细胞介素-6 和硫代巴比妥酸反应性物质水平显著增加。NAC 补充能够减轻炎症和氧化损伤参数，并改善临床评分。总之，NAC 治疗可降低慢性肢体缺血模型中的氧化损伤和炎症，并调节缺氧条件下的氧消耗。
