皮肤再生医疗技术对大鼠慢性难愈合溃疡创面 ERK1/2、ATF2表达的影响

摘要

Objective This article aims to dynamically observe extracellular signal-regulated kinase 1/2 (ERK1/2),activated transcription factor 2 (ATF2)protein expression changes in rats’hard-to-heal wound tissues,and to elucidate the molecular mechanism of skin regenerative medicine and therapy (Moist exposed burn therapy/Moist exposed burn ointment,MEBT/MEBO)in enhancing hard-to-heal ulcer repair from the crosstalk of phosphorylated ERK1/2 activating ATF2. Methods Ninety-six SD rats were randomly divided into 4 groups:MEBO group,rb-bFGF group,model group,and blank control group,24 rats in each group. The superficial skin ulcer models were developed.The healing of wounds was observed.On days 3,7 and 14 after the models were developed,the same location tissues in every rats were collected,then the phosphoryla-ted ERK1/2,ATF2 protein expressions were measured by using Western Blotting. Results The newly pink epitheliums grew from periphery of wounds towards center.The recovery of wounds was fine.Comparison of wound healing time between MEBO group and rb-bFGF group showed there was no statistically significant difference (P >0.05),and both of MEBO group and rb-bFGF group had shorter wound healing time than that of model group (P <0.01).After 14-day treatment,the amount of phosphorylated ERK1/2 and ATF2 elevated;at different time points in the same group the expressions of ERK1/2,ATF2 were statistically differ-ent (P <0.01);at the same time points in different groups the expressions of ERK1/2,ATF2 were statisti-cally different (P < 0.01 );comparison of phosphorylated ERK1/2 and ATF2 expressions between MEBO group and rb-bFGF group showed there was no statistical difference (P >0.05 ),but comparing to model group yielded statistical difference (P <0.01). Conclusion MEBT/MEBO can accelerate the healing process of rats chronic hard-to-heal wounds and improve the healing quality.MEBT/MEBO may regulate phospho-rylated ERK1/2,ATF2 expressions by activating ERK1/2 signaling pathway which induces the crosstalk be-tween ERK1/2 and p38 signaling pathway downstream substrate of ATF2 activated by ERK1/2.%目的：动态观察大鼠难愈性创面组织 ERK1/2、ATF2蛋白表达变化,从磷酸化 ERK1/2对激活 ATF2的交互作用(crosstalk)角度,阐明皮肤再生医疗技术(Moist exposed burn therapy/Moist exposed burn ointment,MEBT/ME-BO)促进慢性难愈合创面修复的分子机制。方法96只 SD 大鼠随机分为 MEBO 组、贝复济(rb-bFGF)组、模型组、空白对照组4组,各24只,创建体表皮肤溃疡模型,观察创面愈合情况,并于造模后第3 d、7 d、14 d 各取相同部位创面组织,采用 Western Blotting 技术检测磷酸化 ERK1/2、ATF2蛋白表达水平。结果 MEBO 组可见淡红色新生上皮由四周向创面中心生长,创面恢复良好。MEBO 组和贝复济组创面愈合时间差异无统计学意义(P >0.05),均小于模型组(P <0.01)；经14 d 治疗后,磷酸化 ERK1/2及 ATF2含量增高,同组内不同时间点 ERK1/2、ATF2的表达差异有统计学意义(P <0.01),同时间点内不同组间的磷酸化 ERK1/2、ATF2的表达差异有统计学意义(P <0.01),组间比较MEBO 组和贝复济组磷酸化 ERK1/2、ATF2的表达差异无统计学意义(P >0.05),但与模型组相比差异有统计学意义(P <0.01)。结论 MEBT/MEBO 能加快大鼠慢性难愈合创面的愈合速度,提高修复质量；MEBT/MEBO 可能通过激活 ERK1/2信号通路,调控磷酸化 ERK1/2、ATF2表达水平,使 ERK1/2激活 p38信号通路的下游底物 ATF2产生交互作用,共同促进慢性难愈合创面的修复。