p38丝裂原活化蛋白激酶和核因子-κB促进创面血管化的机制探讨  

Study of the mechanisms of p38MAPK and NF-κB in promoting angiogenesis in scald wounds

作　　者：吴起[1] 王甲汉[1] 刘亮[1] 李志清[1] 任加良[1] 吴永恒[1] 

机构地区：[1]南方医科大学南方医院烧伤科,广东广州510515

出　　处：《暨南大学学报（自然科学与医学版）》2015年第2期131-135,共5页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：广东省科技计划项目(2013B060300030)

摘　　要：目的:探讨p38丝裂素活化蛋白激酶(MAPK)信号转导通路和核因子-κB(NF-κB)/抑制因子(IκB)通路在调控血管内皮细胞生长因子(VEGF)产生及血管化等方面的作用及其相互关系.方法:将32只Wistar大鼠完全随机分为4组各8只:假烫组、烫伤组、烫伤+p38MAPK抑制剂组和烫伤+NF-κB抑制剂组.除假烫组以外,其余各组均制作深Ⅱ°烫伤模型,其中烫伤+p38MAPK抑制剂组和烫伤+NF-κB抑制剂组于烫伤后15 min和12 h分别静脉注射SB203580和PDTC;各组大鼠均于伤后48 h处死并取材.酶联免疫吸附法(ELISA)测定创面组织中VEGF的含量和血管微密度(MVD),蛋白印迹(Western blotting)法检测p38MAPK和IκBα的表达.结果:和假烫组相比,伤后48 h,烫伤组创面组织中VEGF的质量浓度明显上升,为(0.81±0.19)ng/m L和(2.88±0.32)ng/m L,(P<0.05);MVD值明显增加,为(3.12±0.72)和(8.08±2.10),(P<0.05);p38 MAPK含量升高,为(966±176)和(4778±332),(P<0.05);IκBα含量下降,为(2 327±310)和(1 278±149),(P<0.05).使用SB203580和PDTC均能抑制烧伤后创面组织中VEGF含量的上升和血管化.预先给予SB203580能抑制烧伤后创面组织中p38MAPK含量升高,但对IκBα含量无显著影响;预先给予PDTC可以防止烧伤后创面组织中IκBα含量的下降,而对p38MAPK表达无影响.结论:在烧伤后创面愈合过程中,p38 MAPK信号转导通路和NF-κB/IκB通路是两个平行和独立的信号转导通路,两者间无直接的联系,但共同调节着烧伤后VEGF的产生与创面血管化.Aim：To explore the p38 mitogen-activated protein kinase （MAPK）signal transduction pathway and nuclear factor-κB （NF-κB）/Inhibitory Factor （IκB）pathway in regulation of VEGF pro-duction and angiogenesis and their relationship.Methods：36 adult Wistar rats were randomized into 4 groups：control,scald,scald ＋ SB203580and scald ＋PDTC group,with 8 rats in each group.Except the control group,a deep Ⅱ°scald model was made in each of other groups,of which the scald ＋SB203580 group and the scald ＋PDTC group were injected with SB203580 and PDTC respectively,at 15 min and 12 h after the injury.All rats in each group were sacrificed 48 h after the injury and samples were collected.Enzyme-linked immunosorbent assay （ELISA）was used to determine the vascular endo-thelial growth factor （VEGF）levels and the micro-vascular density （MVD）of the wound tissues.West-ern blot was used to detect the expression of p38MAPK and IκBα.Results：Compared to the control group,in 48h after the scald injury,VEGF was found to be significantly increased in the scald group （as 2.88 ±0.32 ng/mL versus 0.81 ±0.19 ng/mL,P 〈0.05）,and either for MVD （as 8.08 ±2.1 versus 3.12 ±0.72,P 〈0.05）and p38 MAPK levels （966 ±176 and 4 778 ±332,P 〈0.05 ）.However, IκBαwas significantly decreased （as 1278 ±149 versus 2 327 ±310,P 〈0.05）.The results suggested that SB203580 and PDTC inhibited the expression of VEGF and angiogenesis in the wound tissues after the scald injury.Pretreatment with SB203580 could inhibit increase of p38MAPK,but no significant effects were found on the IκBα;pretreated PDTC could prevent decrease of IκBαin the wound tissues,but no effects found on the expression of p38MAPK.Conclusion：During the scald wound healing,p38 MAPK signal transduction pathway and NF-κB /IκB pathway are two parallel and independent signal transduc-tion pathways.There is no direct relationship between the two pathways,although both regulate VEGF production and angiogenesis after scald in

关 键 词：P38 丝裂原活化蛋白激酶 核因子-ΚB VEGF 创面愈合 血管化 

分 类 号：R644[医药卫生—外科学]