Quiroz Yasmir, Ferrebuz Atilio, Romero Freddy, Vaziri Nosratola D, Rodriguez-Iturbe Bernardo
Centro de Investigaciones Biomédicas, Instituto Venezolano de Investigaciones Científicas-Zulia, Maracaibo, Venezuela.
Am J Physiol Renal Physiol. 2008 Feb;294(2):F336-44. doi: 10.1152/ajprenal.00500.2007. Epub 2007 Dec 12.
The progressive deterioration of renal function and structure resulting from renal mass reduction are mediated by a variety of mechanisms, including oxidative stress and inflammation. Melatonin, the major product of the pineal gland, has potent_antioxidant and anti-inflammatory properties, and its production is impaired in chronic renal failure. We therefore investigated if melatonin treatment would modify the course of chronic renal failure in the remnant kidney model. We studied rats followed 12 wk after renal ablation untreated (Nx group, n = 7) and treated with melatonin administered in the drinking water (10 mg/100 ml) (Nx + MEL group, n = 8). Sham-operated rats (n = 10) were used as controls. Melatonin administration increased 13-15 times the endogenous hormone levels. Rats in the Nx + MEL group had reduced oxidative stress (malondialdehyde levels in plasma and in the remnant kidney as well as nitrotyrosine renal abundance) and renal inflammation (p65 nuclear factor-kappaB-positive renal interstitial cells and infiltration of lymphocytes and macrophages). Collagen, alpha-smooth muscle actin, and transforming growth factor-beta renal abundance were all increased in the remnant kidney of the untreated rats and were reduced significantly by melatonin treatment. Deterioration of renal function (plasma creatinine and proteinuria) and structure (glomerulosclerosis and tubulointerstitial damage) resulting from renal ablation were ameliorated significantly with melatonin treatment. In conclusion, melatonin administration improves the course of chronic renal failure in rats with renal mass reduction. Further studies are necessary to define the potential usefulness of this treatment in other animal models and in patients with chronic renal disease.
肾质量减少导致的肾功能和结构的进行性恶化是由多种机制介导的，包括氧化应激和炎症。褪黑素是松果体的主要产物，具有强大的抗氧化和抗炎特性，其分泌在慢性肾衰竭中受损。因此，我们研究了褪黑素治疗是否会改变残余肾模型中慢性肾衰竭的病程。我们研究了肾切除术后未治疗（Nx组，n = 7）以及饮用含褪黑素的水（10 mg/100 ml）治疗（Nx + MEL组，n = 8）并随访12周的大鼠。假手术大鼠（n = 10）用作对照。给予褪黑素使内源性激素水平增加了13 - 15倍。Nx + MEL组大鼠的氧化应激（血浆和残余肾中的丙二醛水平以及肾组织中硝基酪氨酸的丰度）和肾炎症（p65核因子-κB阳性的肾间质细胞以及淋巴细胞和巨噬细胞浸润）减轻。未治疗大鼠残余肾中的胶原蛋白、α-平滑肌肌动蛋白和转化生长因子-β的肾组织丰度均增加，而褪黑素治疗使其显著降低。肾切除导致的肾功能（血浆肌酐和蛋白尿）和结构（肾小球硬化和肾小管间质损伤）恶化经褪黑素治疗得到显著改善。总之，给予褪黑素可改善肾质量减少大鼠的慢性肾衰竭病程。有必要进一步研究以确定这种治疗方法在其他动物模型和慢性肾病患者中的潜在用途。
