Therapeutic strategies of redox modification for renal failure

肾衰竭是一种以突发性（在大多数情况下）可逆性肾功能不全或进行性（在大多数情况下）不可逆性肾功能不全为特征的综合征。诱发因素的范围很广，肾衰竭的病理生理学包括内皮、肾小球和肾小管功能障碍，其严重程度和出现时间各不相同。本课题旨在研究氧化应激和亚硝化应激在体内和体外肾脏损伤中的作用。该项目取得的成果如下。(1)我们已经证明，使用急性肾功能衰竭的大鼠模型，L-Nil（诱导型NO合酶抑制剂），卵磷脂化的SOD，和ebselen（过氧亚硝酸盐的清除剂）治疗改善肾功能，由于其抑制过氧亚硝酸盐的产生或其清除，从而防止脂质过氧化和氧化DNA损伤。(2)我们发现，亚甲基四氢叶酸还原酶（MTHFR）TT基因型可能B ...更多信息 与儿童节段性肾小球硬化的早期发展和进展有关。(3)我们研究了在1型糖尿病早期临床阶段的年轻患者中，晚期糖基化终产物（AGE）的产生和氧化应激是否增加。结果表明，AGEs的积累，其形成与氧化应激密切相关，并导致内皮功能障碍可能在1型糖尿病病程的早期开始。(4)我们使用ECIS技术研究了NO对人微血管内皮细胞粘附的影响。结果表明，NO调节内皮细胞中的细胞-基质和/或细胞-细胞粘附，并且该分子可能改变人体组织和器官中的微血管通透性。(5)本文综述了NO氧化和还原的基本化学问题，并建立了可靠地预测NO（与O_2）在任何时间和任何条件下生成NO_2或N_2O的公式。少

Renal failure is a syndrome characterized by an abrupt, in most cases, reversible kidney dysfunction, or a progressive, in most cases, irreversible kidney dysfunction. The spectrum of inciting factors is broad, and the pathophysiology of renal failure includes endothelial, glomerular and tubular dysfunction, which vary in severity and time of appearance. The present project was designed to examine the contribution of oxidative and nitrosative stress to the renal damage in vivo and in vitro situations. The results obtained with this project are the following.(1) We have demonstrated using the rat model of acute renal failure that L-Nil (inducible NO synthase inhibitor), lecithinized SOD, and ebselen (scavenger of peroxynitrite) treatments improve renal function due to their suppression of peroxynitrite production or its scavenging, consequently preventing lipid peroxidation and oxidative DNA damage.(2) We have found that the methylenetetrahy drofolate reductase (MTHFR) TT genotype may b … More e associated with early development and progression of childhood segmental glomerulosclerosis.(3) We examined whether advanced glycosylation end product (AGE) production and oxidative stress are augmented in young patients with type 1 diabetes at early clinical stages of the disease. The results have indicated that accumulation of AGEs, whose formation is closely linked to oxidative stress, and resultant endothelial dysfunction may start early in the course of type 1 diabetes.(4) We examined the effect of NO on the adhesion of human microvascular endothelial cells using the ECIS technique. The results have suggested that NO modulates cell-matrix and/or cell-cell adhesion in endothelial cells and that this molecule might modify microvascular permeability in human tissues and organs.(5) We have reviewed basic chemical aspects of the oxidation and disproportionation of NO, and also established the formulas for reliably predicting NO_2 or N_2O formation in any set of NO (with O_2) and in any time. Less