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目的 研究雌二醇(Estradiol,E2)对大鼠皮瓣缺血再灌注损伤p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路的影响以及对皮瓣的保护作用.方法 取Wistar大鼠40只,随机分为健康对照组(Ⅰ组)、缺血再灌注组(Ⅱ组)、生理盐水组(Ⅲ组)、E2组(Ⅳ组),每组10只大鼠.分别制作大鼠腹部皮瓣缺血再灌注损伤模型,术后观察各组皮瓣一般情况、测定皮瓣成活率、检测蒂部腹壁浅静脉血清中性粒细胞(NEU)和肿瘤坏死因子α(TNF-α)的浓度.切取皮瓣行组织学观察,并应用Western Blot法检测皮瓣p38 MAPK及丝裂原活化蛋白激酶磷酸酶-2(MKP-2)的表达变化.结果 术后7d皮瓣成活率Ⅳ组显著高于Ⅱ、Ⅲ组(P＜0.05).Ⅳ组蒂部静脉血NEU及TNF-α浓度明显低于Ⅱ、Ⅲ组(P＜0.05).缺血再灌注后,Ⅱ、Ⅲ组p38 MAPK表达明显高于Ⅰ组(P＜0.05),而Ⅳ组p38 MAPK表达较Ⅱ、Ⅲ组显著降低(P＜0.05).Ⅳ组MKP-2表达较Ⅰ、Ⅱ、Ⅲ组均显著增加(P＜0.05).结论 E2可通过抑制p38 MAPK表达,减轻皮瓣内NEU介导的炎性反应级联反应,减少TNF-α释放,从而减轻皮瓣缺血再灌注损伤,提高皮瓣成活率.其作用可能与MKP-2对p38 MAPK活性的抑制有关.“,”Objective To investigate the p38 MAPK changes in flap ischemia reperfusion injury and the protective effect of estradiol (E2).Methods The superficial epigastric artery flap ischemia reperfusion injury model was created in forty adult Wistar rats which were randomly divided into control group (group Ⅰ),ischemiareperfusion group(group Ⅱ),saline group (group Ⅲ),estradiol group (groupiⅣ).The general condition of the flap was observed at 3,5,and 7 days after operation.At 7 days after operation,the survival rate of the flap was detected,the p38 MAPK and MKP-2 expression and protein level were quantified with Westem Blot,the flaps were harvested to perform histology observation and neutrophils (NEU) scoring.The NEU and the TNF-α levels of the superficial epigastric vein were tested.Results The survival rates of the flap 7 days after operation of groupⅣ was higher than group Ⅱ and Ⅲ significantly (P ＜ 0.05).The general and histological observation showed that the degree of inflammatory exudation and necrotic area in the flap edge in group Ⅱ and Ⅲ was more serious than that of groupⅣ at 7 days postoperatively.The NEU and TNF-α in groupⅣ was lower than that in group Ⅱ and Ⅲ (P ＜ 0.05).After ischemia-reperfusion,the p38 MAPK expression in groupⅡ and Ⅲ was significantly higher than that in group Ⅰ (P ＜ 0.05).The expression of p38 MAPK in groupⅣ is lower than that in groupⅡ and Ⅲ (P＜0.05),the MKP-2 expression in groupⅣ is higher than that in group Ⅰ,Ⅱ and Ⅲ (P ＜ 0.05).Conclusion The E2 could inhibit neutrophil infiltration significantly,decrease the TNF-α level in plasma and improve skin flap survival rate by preventing the expression of p38 MAPK.