增生性瘢痕中磷酸化丝裂素活化蛋白激酶蛋白表达的变化

Expression characteristics of phosphorylated forms of mitogen-activated protein kinases in hypertrophic scars

目的 探讨磷酸化细胞外信号调节激酶 1/ 2 (p ERK1/ 2 )、磷酸化应激活化蛋白激酶 (p SAPK)和磷酸化P38MAPK(p P38MAPK)在增生性瘢痕发生和成熟过程中蛋白表达的特征。方法 用免疫组化方法和常规病理技术检测 p ERK1/ 2、p SAPK和p P38MAPK在 16例增生性瘢痕和 8例正常皮肤组织中的表达和分布规律。结果 在正常皮肤中 ,p ERK1/ 2、p SAPK和p P38MAPK主要分布于表皮基底层细胞内 ,三种蛋白的阳性细胞率均较低。随着增生性瘢痕不断成熟 ,p ERK1/ 2和 p SAPK表达逐渐增强。在成熟的增生性瘢痕中 ,这两种蛋白主要存在于表皮基底层细胞和部分成纤维细胞中 ,阳性细胞率分别为正常皮肤的 1 8和 1 7倍 ,蛋白表达明显升高 (P <0 0 5 )。p P38MAPK的阳性细胞率在生长活跃的增生性瘢痕中升至最高 ,在成熟的瘢痕中虽有所下降 ,但仍明显高于正常皮肤(P <0 0 5 ) ,含有 p P38MAPK蛋白的细胞主要为表皮细胞和部分成纤维细胞。结论 在增生性瘢痕中 ,p ERK1/ 2、p SAPK和p P38MAPK蛋白表达均高于正常皮肤 ,提示这三种蛋白介导的信号传导通路可能参与了调控增生性瘢痕的发生和成熟。

Objective To study expression intensity and distribution of phosphorylated forms of extracellular signal-regulated protein kinase1/2 (ERK1/2), stress-activated protein kinase (SAPK) and P38MAPK in normal skin and hypertrophic scars and their potential biological significance. Methods The morphological characteristics of hypertrophic scars in different periods after wound healing and normal skin were examined histopathologically. Protein expression of p-ERK1/2, p-SAPK and p-P38MAPK was also assessed with immunohistochemical technique. Results In normal skin, phosphorylated forms of ERK1/2, SAPK and P38MAPK were mainly located in epidermal basal cells, in which the positive cellular rates of all the three proteins were low. Along with the maturation of hypertrophic scars, protein contents of p-ERK1/2 and p-SAPK were progressively increased. In mature hypertrophic scars, positive signals of these two proteins were mostly distributed in keratinocytes and some fibroblasts. The positive cellular rate of p-P38MAPK ascended in active hypertrophic scar, then decreased to a level which was still higher than that of normal skin. Conclusion The formation of hypertrophic scars may be associated with the alteration in signaling pathways which results in the increment of protein contents of p-ERK1/2, p-SAPK and p-P38MAPK.