基质金属蛋白酶及其抑制因子在胎儿皮肤内的表达特征及其意义

目的探讨基质金属蛋白酶-2（MMP-2）、MMP-3、MMP-9及金属蛋白酶组织抑制因子-1（TIMP-1）、TIMP-2在不同发育时期胎儿皮肤中的表达特征及其可能的生物学意义。方法24例被测标本中包括不同胎龄（12～40周）的胎儿皮肤。用免疫组化方法和病理技术检测这5种蛋白在胎儿皮肤中定位和表达量的变化规律。结果MMP-2、MMP-3、MMP-9、TIMP-1和TIMP-2在不同时期的胎儿皮肤内均有表达，它们主要分布于表皮细胞、成纤维细胞、毛囊和汗腺上皮细胞以及血管内皮细胞的胞浆中。在早期（胎龄12～18周）妊娠胎儿皮肤中，MMP-2、MMP-3、MMP-9蛋白呈强阳性表达，随着胎儿生长发育，这些蛋白的阳性率逐渐降低，在晚期（胎龄27～40周）妊娠胎儿皮肤中这些蛋白的阳性细胞率均明显低于早期妊娠胎儿（P均〈0．05）。TIMP-1和TIMP-2呈相反的变化规律，在早期妊娠胎儿皮肤中表达水平较低，而在晚期妊娠胎儿皮肤中这两种蛋白阳性细胞率增大，显著高于早期妊娠胎儿（P均〈0．05）。结论MMP-2、MMP-3、MMP-9、TIMP-1和TIMP-2可能对皮肤的发生、结构功能的维持以及创伤后修复起重要作用。在早期妊娠胎儿皮肤中，MMP-2、MMP-3、MMP-9高表达以及TIMP-1和TIMP-2低表达可能与胎儿皮肤创面无瘢痕愈合密切相关。

Expression of matrix metalloproteinases and their inhibitors in fetal skin and their biological significance

Objective To investigate the expression characteristics of matrix metalloproteinases (MMP-2, MMP-3, MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) in developing fetal skin and their potential biological significance.Methods Skin of 24 cases of fetuses with different gestational age (12-40 weeks) were obtained, embedded with paraffin wax, and sectioned. Immunohistochemistry and pathological methods were used to detect the expression intensity and distribution of MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2. Results Positive immunohistochemical signals of MMPs and TIMPs could be found in fetal skin at different gestational periods.These proteins mainly located in the cytoplasm of epidermal cells, fibroblasts, epithelial cells of hair follicles and sweat glands and vascular endothelial cells.In earlier gestational fetal skin (12-18 weeks), the expression levels of MMP-2, MMP-3 and MMP-9 were high. Along with the advancement in gestational age, the positive rates of these three proteins in skin were lowered, and in later gestational fetal skin (27-40 weeks) the expression rates were significantly decreased compared with those in earlier gestational fetal skin (all P<0.05). On the contrary , protein expression levels of TIMP-1 and TIMP-2 were apparently lower in earlier versus later gestational skin (both P<0.05). Conclusion MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2 might be involved in the skin development and maintenance of cutaneous structure and function. Higher expression of MMP-2, MMP-3 and MMP-9 and lower protein levels of TIMP-1 and TIMP-2 may provide an antiscarring signal in healing of wound during early periods of gestation.