雌二醇对大鼠皮瓣缺血再灌注损伤p38丝裂原活化蛋白激酶信号通路影响的实验研究  

Experimental study on influence of estradiol on p38 MAPK in flap ischemia reperfusion injury

作　　者：吴建龙[1] 巨积辉[1] 周广良[1] 刘跃飞[1] 张广亮[1] 侯瑞兴[1] 

机构地区：[1]苏州大学附属瑞华医院手外科,江苏215104

出　　处：《中华手外科杂志》2015年第2期138-141,共4页Chinese Journal of Hand Surgery

摘　　要：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（1I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a（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p38MAPK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p38MAPK表达明显高于I组（P〈0．05），而Ⅳ组038MAPK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p38MAPK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038MAPK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 ）, ischemia- reperfusion group（group Ⅱ ）, saline group （group Ⅲ ）, estradiol group （ group Ⅳ ）. 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 Western 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 sttrvival rates of the flap 7 days after operation of group Ⅳ 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 11 and Ⅲ was more serious than that of group Ⅳ at 7 days postoperatively. The NEU and TNF-α in grouplV was lower than that in groupⅡ and Ⅲ （ P 〈0.05）. After ischemia-reperfusion, the p38 MAPK expression in groupⅢ 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 groupⅢ and Ⅲ （P 〈0.05）, the MKP-2 expression in groupⅣ is higher than that in group I , Ⅱ and m （ 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 1938 MAPK.

关 键 词：外科皮瓣 再灌注损伤 雌二醇 P38丝裂原活化蛋白激酶 

分 类 号：R364.5[医药卫生—病理学]