α促黑素细胞激素对横纹肌溶解所致急性肾衰竭大鼠肾的保护作用

α-melanocyte-stimulation hormone reduces renal inflammation and protects renal function in rhabdomyolysis-induced acute renal failure rats

目的探讨α促黑素细胞激素（α—MSH）是否能减轻甘油诱导横纹肌溶解所致急性。肾衰竭（ARF）大鼠。肾组织中炎性反应和对。肾损害的保护作用。方法48只SD大鼠随机分4组：健康对照组：肌注生理盐水10ml／kg；ARF组;肌注50％甘油10ml／kg；α-MSH立即干预组：肌注50％甘油的同时腹腔注射α—MSH200μg／kg，12h后重复1次；α-MSH延迟干预组：肌注50％甘油6h后腹腔注射α—MSH200μg／kg，12h后重复1次。24h后处死大鼠，测Scr、BUN、肌酸激酶水平。。肾组织PAS染色光镜下行。肾小管坏死半定量评分。免疫组化ED-1染色半定量计数。实时定量PCR测。肾组织中单核细胞趋化因子（MCP）-1mRNA表达水平。结果与对照组相比，ARF组大鼠。肾组织内ED．1染色阳性细胞数（16．8±7．0比1．46＋1．24）、MCP-1的mRNA表达量（11．0±3．8比7．8±1．9）均显著增加（P均〈0．05）。α-MSH立即干预组ED-1染色阳性细胞数（9．5±8．2）和MCP．1的mRNA表达量（8．7±5．1）与ARF组相比均显著减少（P〈0．05）。α—MSH立即干预组Scr、BUN和。肾小管坏死评分均低于ARF组【分别为（152±76）比（333±60）μmol／L、（23．8±9．3）比（56．0±10．0）mmol／L和1．7±0．4比2．7±0．4，P均〈0．05]。而α-MSH延迟干预组与ARF组间各指标及各组间血IL．6和TNF—α差异均无统计学意义。结论甘油所致急性。肾衰竭大鼠。肾组织中巨噬细胞浸润及MCP-1表达增加，即刻注射α-MSH有一定的抑制。肾组织炎性反应、减轻。肾损害作用。

Objective To investigate the effects of α-MSH on kidney inflammation and renal function of rhabdomyolysis-induced acute renal failure （ARF） by glycerol in rats. Methods Forty-eight Sprague-Dawley rats were divided into four groups： normal control group received 10 ml/kg saline by i.m.. ARF group rats were injected with 50% glycerol （10 ml/kg, i.m.）, α-MSH immediate group and α-MSH delayed group were respectively given α-MSH （200 μg/kg, i.p.） immediately or 6 h afterward in addition to 50% glycerol injected （10 ml/kg, i.m.）, and repeated after 12 h. Blood samples and kidney tissues were taken from anaesthetised rats at 24 h. Plasma creatine kinase （CK）, BUN, Scr, IL-6 and TNF-α levels, as well as kidney acute tubular necrosis scores, ED-1 cell, and MCP-1 mRNA expression were investigated. Results Kidney tissues of ARF rats had more ED-1 positive cells （1.46±1.24 vs. 16.8±7.0, P〈0.05）and higher MCP-1 mRNA expression （7.8±1.9 vs. 11.0±3.8, P〈0.05） compared with normal control rats. α-MSH immediate group had less ED-1 positive cells （9.5±8.2） and lower MCP-1 mRNA expression （7.8±5.1） in kidney compared with ARF group （P〈O.05）. Also compared with ARF group, α-MSH immediate group had a lower BUN [（23.8±9.3） vs. （56.0±10.0） mmol/L, P〈0.05], lower Scr [（152±76） vs. （333±60） Ixmol/L, P〈O.05] and lower ATN score（1.7±0.4 vs. 2.7±0.4, P〈O.05）. There were no significant differences of above parameters between α-MSH delayed group and ARF group. Conclusion There is obvious inflammation in kidneys of rhabdomyolysis-induced ARF rats, and α-MSH immediately administration can attenuate the inflammation and prαect acute renal injury.