Stacchiotti Alessandra, Rezzani Rita, Angoscini Paola, Rodella Luigi, Bianchi Rossella
Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Histochem J. 2002 Jun-Jul;34(6-7):305-12. doi: 10.1023/a:1023378525471.
Small heat shock proteins (sHSPs) are cytoskeletal chaperones constitutively expressed in the normal kidney but enhanced with beneficial roles during adverse stimuli. Cyclosporine A is an immunosuppressive drug with major adverse side effect such as severe nephrotoxicity. Among possible mechanisms of cyclosporine A-induced renal damage, oxidative stress and cytoskeletal damage have been suggested. Melatonin has been successfully used as antioxidant against many renal diseases. This in vivo study was performed to shed light on the protective effect of melatonin against cyclosporine A-induced renal alterations. We treated rats with cyclosporine A alone, or combined with melatonin, and with melatonin alone (as controls) for 40 days and analysed the renal abundance and distribution of two sHSPs, HSP25 and alpha B-crystallin. These data were correlated with the histopathological effects of the treatments. Cyclosporine A induced insoluble isoforms that moved to soluble fractions after melatonin coadministration as in controls. After cyclosporine A treatment, an intense signal for sHSPs was found within the glomeruli, nucleus and cytoplasm of cortical tubules, collecting ducts and vascular wall. After melatonin supply, the staining was faint, limited to the cytoplasm of cortical tubules, similar to controls. Both fibrosis and tubular alterations significantly decreased after melatonin coadministration. In conclusion, HSP25 and alpha B-crystallin are overexpressed in the rat kidney treated with cyclosporine A but are similar to controls after combined melatonin. This could be a consequence of the cytoprotective effect of melatonin in this nephrotoxic model so that a beneficial sHSPs response is unnecessary.
小热休克蛋白（sHSPs）是正常肾脏中组成性表达的细胞骨架伴侣蛋白，在不良刺激下表达增强并发挥有益作用。环孢素A是一种免疫抑制药物，具有严重肾毒性等主要不良副作用。在环孢素A诱导肾损伤的可能机制中，氧化应激和细胞骨架损伤被认为是相关因素。褪黑素已成功用作抗多种肾脏疾病的抗氧化剂。本体内研究旨在阐明褪黑素对环孢素A诱导的肾脏改变的保护作用。我们将大鼠分别单独用环孢素A处理、或与褪黑素联合处理、以及单独用褪黑素处理（作为对照）40天，并分析了两种小热休克蛋白HSP25和αB-晶状体蛋白在肾脏中的丰度和分布。这些数据与处理的组织病理学效应相关。环孢素A诱导了不溶性异构体，与对照组一样，在联合给予褪黑素后这些异构体转变为可溶性组分。环孢素A处理后，在肾小球、皮质肾小管的细胞核和细胞质、集合管以及血管壁中发现了小热休克蛋白的强烈信号。给予褪黑素后，染色变淡，仅限于皮质肾小管的细胞质，与对照组相似。联合给予褪黑素后，纤维化和肾小管改变均显著减少。总之，HSP25和αB-晶状体蛋白在环孢素A处理的大鼠肾脏中过度表达，但联合褪黑素处理后与对照组相似。这可能是褪黑素在这种肾毒性模型中具有细胞保护作用的结果，因此不需要有益的小热休克蛋白反应。
