中文摘要：

目的 探讨富马酸二甲酯（DMF）在小鼠肾脏缺血再灌注损伤中的保护作用及可能的机制。方法 将小鼠随机分成3组（n=8）：假手术组（S组）、缺血再灌注组（IR组）和DMF预处理组（DMF组）。IR组及DMF组制备肾脏IR模型,再灌注24h后收集血清及肾组织,测定血清肌酐（SCr）及尿素氮（BUN）值;评定肾脏组织形态学改变;检测肾脏组织中丙二醛（MDA）含量及超氧化物歧化酶（SOD）活力;Western-blot检测各组肾组织内核因子E2相关因子2（Nrf2）及血红素氧化酶-1（HO-1）蛋白含量。结果IR组SCr及BUN显著高于S组[（143.17±14.18）μmol/L,（26.52±3.56）mmol/L vs.（24.50±5.54）μmol/L,（8.25±2.14）mmol/L,P〈0.01];DMF组SCr及BUN均低于IR组[（81.83±9.39）μmol/L,（18.62±2.75）mmol/L vs.（143.17±14.18）μmol/L,（26.52±3.56）mmol/L]（P〈0.01）;和IR组比较,DMF组的组织形态学损伤较轻（P〈0.01）;DMF组过氧化损伤指标MDA水平低于IR组[（3.55±0.48）μmol/g vs.（5.48±0.70）μmol/g]（P〈0.01）,而抗氧化酶SOD水平高于IR组[（35.02±4.13）kU/g vs.（23.80±4.36）kU/g]（P〈0.01）。Western-blot及免疫组化结果显示DMF组Nrf2和HO-1蛋白表达水平高于IR组（P〈0.05）。结论 DMF对小鼠肾缺血再灌注损伤具有保护作用,其机制可能与激活Nrf2/HO-1通路进而提高肾脏抗氧化应激能力有关。

英文摘要：

ObjectiveTo explore the potential role of dimethyl fumarate（DMF） on renal ischemia-reperfusion injury （IRI） and its mechanisms.MethodsTwenty-four male C57BL/6 mice were randomly divided into three groups of 8 animals each： Sham group（group S）,IR group（group IR） and DMF pretreatment ＋IR group（group DMF）.The model of renal ischemia-reperfusion was established in group IR and group DMF.The levels of serum creatinine （SCr） and blood urea nitrogen （BUN） were determined.The renal injury was observed by PAS staining.The content of malondialdehyde （MDA） and the activity of superoxide dismutase （SOD） were tested.The levels of nuclear factor erythroid 2-related factor 2（Nrf2） and heme oxygenase（HO）-1 protein in renal tissues were detected using western-blot and immunohistochemical staining（IHC）.ResultsThe levels of SCr and BUN in IR group were significantly increased than those in Sham group[（143.17±14.18） μmol/L,（26.52±3.56） mmol/L vs.（24.50±5.54） μmol/L,（8.25±2.14） mmol/L]（P〈0.01）; The levels of Cr and BUN in DMF group [（81.83±9.39） μmol/L,（18.62±2.75） mmol/L] were lower than those in IR group [（143.17±14.18） μmol/L,（26.52±3.56）mmol/L （P〈0.01）.Renal tubular injury scores in DMF group were also decreased than those in IR group（P〈0.01）.The MDA level in DMF group was lower than those in IR group [（3.55±0.48） μmol/g vs.（5.48±0.70） μmol/g,P〈0.01） ].The SOD activitiys in DMF group was higher than those in IR group [ （35.02±4.13） kU/g vs.（23.80±4.36） kU/g,P〈0.01） ].Western-blot and IHC showed that the expression of Nrf2 and HO-1 protein in DMF group were significantly upregulated as compared with IR group（P〈0.05）.ConclusionsDMF can protect against renal ischemia-reperfusion injury,which may be through the activation of Nrf2/HO-1 signaling pathway.