CAJ | 학술논문

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／mL 和（2.88±0.32）ng／mL，（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（2327±310）和（1278±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．
목적：탐토 p38사렬소활화단백격매（MAPK）신호전도통로화핵인자-κB（NF-κB）／억제인자（IκB）통로재조공혈관내피세포생장인자（VEGF）산생급혈관화등방면적작용급기상호관계．방법：장32지 Wistar 대서완전수궤분위4조각8지：가탕조、탕상조、탕상＋p38MAPK 억제제조화탕상＋NF-κB 억제제조．제가탕조이외，기여각조균제작심Ⅱ°탕상모형，기중탕상＋p38MAPK 억제제조화탕상＋NF-κB 억제제조우탕상후15 min 화12 h 분별정맥주사 SB203580화 PDTC；각조대서균우상후48 h 처사병취재．매련면역흡부법（ELISA）측정창면조직중 VEGF적함량화혈관미밀도（MVD），단백인적（Western blotting）법검측 p38MAPK 화 IκBα적표체．결과：화가탕조상비，상후48 h，탕상조창면조직중 VEGF 적질량농도명현상승，위（0.81±0.19）ng／mL 화（2.88±0.32）ng／mL，（P ＜0.05）；MVD 치명현증가，위（3．12±0．72）화（8．08±2．10），（P ＜0.05）；p38 MAPK 함량승고，위（966±176）화（4778±332），（P ＜0.05）；IκBα함량하강，위（2327±310）화（1278±149），（P ＜0.05）．사용 SB203580화 PDTC 균능억제소상후창면조직중 VEGF 함량적상승화혈관화．예선급여 SB203580능억제소상후창면조직중 p38MAPK 함량승고，단대 IκBα함량무현저영향；예선급여 PDTC 가이방지소상후창면조직중 IκBα함량적하강，이대 p38MAPK표체무영향．결론：재소상후창면유합과정중，p38 MAPK 신호전도통로화 NF-κB／IκB 통로시량개평행화독립적신호전도통로，량자간무직접적련계，단공동조절착소상후 VEGF 적산생여창면혈관화．
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 injuries.