依达拉奉对大鼠肾脏缺血再灌注损伤的保护作用及与缺血后处理的比较研究(英文)

Protective effect of edaravone against renal ischemia/reperfusion injury and compared with ischemic postconditioning in rats

阐明依达拉奉是否对大鼠肾脏缺血再灌注损伤有保护作用,并且比较依达拉奉后处理与缺血后处理的保护作用。大鼠缺血45min再灌注24h。56只大鼠随机分为以下7组:假手术组、缺血再灌注组、缺血后处理组、生理盐水后处理组以及依达拉奉(1,3和6mg·kg-1)后处理组。通过测定血清尿素氮和肌酐浓度来评价肾功能,肾脏组织学损伤通过苏木素-伊红染色进行评价。通过测定肾组织中的丙二醛含量和超氧化物歧化酶活性来评估氧化应激损伤;TUNEL法检测肾小管上皮细胞凋亡;免疫印迹法检测肾组织中的Bcl-2和Bax的蛋白水平。与缺血再灌注组相比,依达拉奉后处理明显降低血清尿素氮和肌酐浓度,并且可以改善肾组织损伤。依达拉奉后处理组的丙二醛含量比缺血再灌注组低,而依达拉奉后处理组的超氧化物歧化酶活性比缺血再灌注组高。然而,依达拉奉后处理也能够降低细胞凋亡和Bax的表达,增加Bcl-2的表达。依达拉奉后处理组与缺血后处理组所检测的结果没有统计学差异。以上结果说明,在缺血最后3min、再灌注前通过尾静脉注射依达拉奉,可以诱导药物后处理防治肾脏的缺血再灌注损伤,而且这种保护作用与观察到的缺血后处理的保护作用相似。

The aim of this study is to clarify whether edaravone postconditioning had protective effect against renal ischemia/reperfusion injury and to compare the protective effect between ischemic postconditioning and edaravone postconditioning.Rats were subjected to 45 min ischemia followed by 24 h reperfusion.The rats were randomly assigned to seven groups：a sham-operated control group,an ischemia/reperfusion group,an ischemic postconditioning group,a normal saline vehicle postconditioning group and an edaravone postconditioning（1,3,and 6 mg·kg-1） group.Renal function was assessed by serum creatinine and BUN concentration,while histological damage of renal tissue was assessed with HE staining.MDA content and SOD activity of renal tissue were determined.TUNEL staining was performed to analyze the apoptosis of the tubular epithelial cells,the protein level of Bcl-2 and Bax in renal tissue was examined by Western blotting.Compared to the ischemia/reperfusion group,edaravone postconditioning significantly decreased serum creatinine and BUN concentration,and ameliorated histological damage of renal tissue.MDA was less after 24 h reperfusion in the edaravone postconditioning group than that in the ischemia/reperfusion group,consistent with an increase in SOD activity.In addition,edaravone postconditioning decreased TUNEL-positive cells and Bax expression,and increased Bcl-2 expression.Results detected in the edaravone postconditioning group showed no significant difference from the ischemic postconditioning group.Edaravone administered during the last 3 min of ischemia,prior to reperfusion induces a pharmacological postconditioning in vivo against renal ischemia/reperfusion injury in rats.This protection is similar to that observed with ischemic postconditioning.