Lee Y S, Park J J, Chung K Y
Division of Nephrology, the Eulji University Hospital, Seoul, South Korea.
Transplant Proc. 2008 Sep;40(7):2142-4. doi: 10.1016/j.transproceed.2008.07.101.
alpha-Melanocyte stimulating hormone (alpha-MSH) may ameliorate renal ischemia-reperfusion (I/R) injury. Recent data suggest that melanocortin receptors may be related to the anti-inflammatory and immunomodulating action for alpha-MSH. We designed this experiment to determine the renal distribution of alpha-MSH receptors; melanocortin-1 receptor (MC-1R) and melanocortin-3 receptor (MC-3R).
Sprague-Dawley male rats (n = 24) were randomly divided into 2 groups: the sham (n = 2) and the operation groups with warm ischemia (n = 12). Animals in the operation group were subjected to 40 minutes of warm renal ischemia. Western blotting analyses and immunohistochemistry were employed to determine expression of MC-1R and MC-3R.
Expression of MC-1R and MC-3R was decreased on 1 day after reperfusion. Immunohistochemical study confirmed the findings of Western blot analysis.
The present study demonstrated novel renal expression of MC-1R and MC-3R, especially in the outer medulla, representative of the renal I/R injury. Our current study suggested that the mechanisms of action of alpha-MSH may significantly attenuate the renal I/R injury by specific kidney-targeted effects via MC-Receptors as well as by systemic cytokine effects.
α-黑素细胞刺激素(α-MSH)可能改善肾缺血再灌注(I/R)损伤。最近的数据表明,黑皮质素受体可能与α-MSH的抗炎和免疫调节作用有关。我们设计了本实验以确定α-MSH受体;黑素皮质素-1受体(MC-1R)和黑素皮质素-3受体(MC-3R)在肾脏中的分布。
将24只雄性Sprague-Dawley大鼠随机分为2组:假手术组(n = 2)和热缺血手术组(n = 12)。手术组动物经历40分钟的热肾缺血。采用蛋白质印迹分析和免疫组织化学方法测定MC-1R和MC-3R的表达。
再灌注1天后,MC-!R和MC-3R的表达降低。免疫组织化学研究证实了蛋白质印迹分析的结果。
本研究证实了MC-1R和MC-3R在肾脏中的新表达,尤其是在肾外髓质,这是肾I/R损伤的典型表现。我们目前的研究表明,α-MSH的作用机制可能通过MC受体的特异性肾脏靶向效应以及全身细胞因子效应显著减轻肾I/R损伤。