摘要
目的:探讨原癌基因c-fos在伤后皮肤创面愈合过程中的调控作用及其对修复结局的影响。方法:利用大鼠深Ⅱ°烫伤模型,采用免疫组化和原位杂交方法分别检测PCNA蛋白及bFGF mRNA在创面组织中的表达,并观察外源性使用c-fos单克隆抗体及bFGF后二者表达的变化规律及修复结局的改变。结果:烧伤诱导c-fos及bFGF mRNA的表达,从而启动修复过程。外源性应用c-fos抗体后,伤后各时间点基本探测不到bFGFmRNA的表达,伤后14d创面皮肤虽然基本完成了再上皮化过程,但其基底细胞排列成薄层细胞,PCNA数密度明显低于对照组,同时皮肤全层变薄。而创面外源性应用bFGF后,bFGF mRNA表达有一定增加,但无明显差异。但伤后14d创面皮肤组织基底层变厚,其中含有大量PCNA阳性细胞,真皮层亦变厚,并含有大量的毛细血管。结论:c-fos在创面愈合过程中具有重要作用,它可以启动bFGF基因转录,增加细胞的增殖活性。用c-fos抗体中和内源性c-fos作用可以明显抑制生长相关基因的表达,最后导致创面修复细胞PCNA表达下降。
Objective: To investigate the important network regulation of c-fos and bFGF in wound healing process and its relation with wound repair. Methods: In situ hybridization and immunohistochemistry were used to detect the expression of bFGF mRNA and proliferating cell nuclear antigen (PCNA) in the normal and burned rat skin at 3h, 6h, 1d, 3d, 7d and 14d postinjury in a partial thickness burn model. The effects of c-fos antibody and exogenous basic fibroblast growth factor on their changes were also investigated. Results: Endogenous bFGF mRNA could not be detected after c-fos antibody treatment during the whole postburn course. The bFGF mRNA expression increased little after exogenous treatment with bFGF. Treatment with c-los antibody could significantly decrease the expression of proliferating cell nuclear antigen (PCNA). Though the re-epithelial process was almost completed on 14d posthurn, the thickness of basal cells was thinner than that in controls. Microscopic observation showed that the skin thickness decreased about 1/3 compared with simple controls. After treatment with bFGF, the basal cells grew thicker, and there were more PCNA-positive cells, and the wounded area contained abundant capillaries. Conclusion: c-fos plays an important role in wound healing process. It can promote transcription of bFGF gene, increase cell activity and the number of proliferating cells. Treatment with c-fos antibody to neutralize the endogenous c-los expression may inhibit the expression of genes of growth-related factors, and decrease cell proliferation in wound area.
出处
《感染．炎症．修复》
2000年第1期34-37,共4页
Infection Inflammation Repair
基金
国家重大基础研究发展规划(G1999054204)
国家杰出青年科学基金(39525024)
