Manucha Walter
área de Farmacología, Departamento de Patología, Facultad de Ciencias Médicas. Universidad Nacional de Cuyo, Mendoza, Argentina. E-mail:
Medicina (B Aires). 2014;74(3):254-8.
The apoptosis and renal fibrosis are processes inherent to the chronic kidney disease, and consequently a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with chronic renal disease associated to an increase of the oxidative stress. The injured tubular cells linked to the interstitial macrophages and myofibroblasts produce cytokines and growth factors that encourage an inflammatory condition, inducing the apoptosis of the tubular cells and enabling the accumulation of the extracellular matrix. The angiotensin II has a central role in the renal fibrogenesis leading to a rapid progression of the chronic kidney disease. The growing levels of the angiotensin II induce pro-inflammatory cytokines, the activation of NF-kB, adhesion molecules,chemokines, growth factors, and oxidative stress. The current evidence suggests that the angiotensin II increases the mitochondrial oxidative stress, regulates the induction of the apoptosis and conditions the inflammatory process. Therefore the mitochondria and the oxidative stress would play a determinant role in the renal inflammatory process. Finally, this review summarizes our present knowledge regarding the possible mechanisms that would contribute to the apoptosis conditioned by inflammation and/or oxidative stress during the chronic renal disease. Additionally, a new concept of the anti-inflammatory tools is proposed to regulate the mitochondrial oxidative stress that would directly affect the inflammatory process and apoptosis. This concept could have positive consequences on the treatment of renal inflammatory pathologies and related diseases.
细胞凋亡和肾纤维化是慢性肾脏病的固有过程，因此，在与氧化应激增加相关的慢性肾脏病患者中，已发现线粒体呼吸机制明显失调。与间质巨噬细胞和成肌纤维细胞相关的受损肾小管细胞会产生细胞因子和生长因子，从而引发炎症状态，诱导肾小管细胞凋亡，并促使细胞外基质积聚。血管紧张素II在肾纤维化形成过程中起核心作用，导致慢性肾脏病迅速进展。血管紧张素II水平的升高会诱导促炎细胞因子、核因子κB激活、黏附分子、趋化因子、生长因子以及氧化应激。目前的证据表明，血管紧张素II会增加线粒体氧化应激，调节细胞凋亡的诱导并影响炎症过程。因此，线粒体和氧化应激在肾脏炎症过程中起决定性作用。最后，本综述总结了我们目前关于在慢性肾脏病期间可能导致炎症和/或氧化应激诱导细胞凋亡的机制的认识。此外，还提出了一种新的抗炎工具概念，以调节线粒体氧化应激，这将直接影响炎症过程和细胞凋亡。这一概念可能对肾脏炎症性疾病及相关疾病的治疗产生积极影响。
