p38MAPK信号通路参与雌二醇减轻皮瓣缺血再灌注损伤机制的初步研究
发布时间：2018-08-01 15:36
【摘要】：目的:p38丝裂原活化蛋白激酶(p38MAPK)信号通路是哺乳动物细胞中调控炎症、细胞增殖与凋亡等最重要的信号通路之一。p38MAPK在细胞内可被周围环境中的应激刺激、炎性因子等激活,在缺血再灌注损伤的发生和发展过程中起到非常重要的作用。本文旨在通过探讨雌二醇(Estradiol,E2)对皮瓣内p38MAPK信号通路的影响及p38MAPK信号通路在皮瓣缺血再灌注损伤中的作用,为雌二醇治疗皮瓣缺血再灌注损伤提供理论依据。方法:Wistar大鼠48只,雄性,12~14周,在无特定病原菌级(SPF级)实验室条件下,建立大鼠腹部皮瓣缺血再灌注损伤模型。随机将大鼠分为对照组(Ⅰ组):皮瓣切取后不作缺血再灌注处理,即刻原位缝合皮瓣;缺血再灌注组(Ⅱ组):切取皮瓣后,用无损伤显微血管夹夹闭腹壁浅动静脉6h后取出血管夹,确认腹壁浅动静脉血流恢复后,同法缝合皮瓣;生理盐水组(Ⅲ组):同Ⅱ组建立皮瓣模型后,腹腔注射生理盐水;E2组(Ⅳ组):同Ⅱ组建立皮瓣模型,腹腔注射E2。术后观察各组皮瓣一般情况;对皮瓣进行摄像,采用Image-Pro Plus.V6.0图像分析系统计算皮瓣存活率;抽取皮瓣蒂部腹壁浅静脉血,检测血清中性粒细胞(neutrophils,NEU)数量、TNF-α及IL-10浓度;切取皮瓣行组织学观察,应用免疫组织化学染色及Western Blot法检测p38 MAPK及丝裂原活化蛋白激酶磷酸酶-2(MKP-2)的表达情况。结果:术后7d,大鼠皮瓣存活率Ⅳ组显著高于Ⅱ、Ⅲ组(P0.05)。Ⅳ组蒂部静脉血NEU数量及TNF-α浓度明显低于Ⅱ、Ⅲ组(P0.05),而IL-10浓度显著高于Ⅱ、Ⅲ组(P0.05)。皮瓣组织学与超微结构检查结果显示:与Ⅱ组、Ⅲ组相比,Ⅳ组皮瓣炎性渗出明显较少,组织结构完整,细胞变性、坏死现象少见,细胞内细胞器更加完整。Western Blot结果与免疫组化结果一致,显示:Ⅱ、Ⅲ组p38MAPK表达明显高于Ⅰ组(P0.05),而Ⅳ组p38MAPK表达较Ⅱ、Ⅲ组显著降低(P0.05)。Ⅳ组MKP-2表达较Ⅰ、Ⅱ、Ⅲ组均显著增加(P0.05)。相关性结果显示:皮瓣存活率与NEU数量、TNF-α浓度之间均显著负相关。结论:1.雌二醇可明显抑制皮瓣内NEU介导的炎症级联反应,减少TNF-α等促炎介质释放,增强组织抗炎功能,保护皮瓣内微循环血流灌注,从而减轻皮瓣缺血再灌注损伤引起的病理生理变化,增强皮瓣活力,促进皮瓣存活。为雌二醇治疗皮瓣缺血再灌注损伤提供了新的证据和方向。2.雌二醇可显著抑制皮瓣组织中p38MAPK的蛋白表达,而增加MKP-2的蛋白表达,提示雌二醇可通过阻滞MAPK的炎症信号级联通路,调控细胞内促炎性基因的表达,减轻皮瓣组织内炎症反应,该过程可能与MKP-2抑制p38MAPK的活性有关。
[Abstract]:Objective: p38 mitogen-activated protein kinase (p38MAPK) signaling pathway is one of the most important signaling pathways in mammalian cells to regulate inflammation, cell proliferation and apoptosis. It plays an important role in the occurrence and development of ischemia-reperfusion injury. The purpose of this study was to investigate the effects of estradiol (E 2) on the p38MAPK signal pathway in the flap and the role of the p38MAPK signal pathway in the ischemia reperfusion injury of the flap, and to provide a theoretical basis for the treatment of the flap ischemia reperfusion injury by estradiol. Methods Forty-eight male Wistar rats were used to establish the model of abdominal flap ischemia-reperfusion injury under the condition of no specific pathogenic bacteria (SPF grade) in the laboratory for 14 weeks. The rats were randomly divided into control group (group 鈪，
本文编号：2158035
[Abstract]:Objective: p38 mitogen-activated protein kinase (p38MAPK) signaling pathway is one of the most important signaling pathways in mammalian cells to regulate inflammation, cell proliferation and apoptosis. It plays an important role in the occurrence and development of ischemia-reperfusion injury. The purpose of this study was to investigate the effects of estradiol (E 2) on the p38MAPK signal pathway in the flap and the role of the p38MAPK signal pathway in the ischemia reperfusion injury of the flap, and to provide a theoretical basis for the treatment of the flap ischemia reperfusion injury by estradiol. Methods Forty-eight male Wistar rats were used to establish the model of abdominal flap ischemia-reperfusion injury under the condition of no specific pathogenic bacteria (SPF grade) in the laboratory for 14 weeks. The rats were randomly divided into control group (group 鈪，
本文编号：2158035
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