GRP94在人增生性瘢痕组织中的表达及曲安奈德对其影响

Expression of GRP94 in hypertrophic scar and the effect of triamcinolone acetonide

目的观察GRP94在人增生性瘢痕组织中的表达及曲安奈德对其影响,探讨GRP94在增生性瘢痕形成中的作用。方法以10例正常皮肤组织作为对照,采用免疫组化法和免疫印迹法检测10例增生性瘢痕组织中GRP94蛋白的表达;建立人增生性瘢痕移植于裸鼠的模型,以注射生理盐水作为对照,采用免疫组化法检测曲安奈德对GRP94表达的影响。结果①GRP94主要在增生性瘢痕和正常皮肤组织的角质形成细胞、成纤维细胞、血管内皮细胞和炎症细胞的胞浆表达,在少数细胞的胞核中也有表达;在正常皮肤的毛囊、汗腺、皮脂腺中表达。②GRP94在增生性瘢痕和正常皮肤组织中的表达:在表皮中,两者比较其差异无统计学意义(P>0.05);在真皮中,增生性瘢痕组的GRP94阳性成纤维细胞数(731.67±148.31/mm2)高于正常皮肤组(202.00±188.43/mm2),两者比较,其差异有统计学意义(P<0.05)。免疫印迹结果进一步证实,增生性瘢痕组的GRP94含量(0.43±0.25)高于正常皮肤组(0.14±0.03),两者比较,其差异有统计学意义(P<0.05)。③注射曲安奈德后,增生性瘢痕组织的GRP94阳性成纤维细胞数(平均值为247.50±81.82/mm2)显著减少,与对照组(平均值为485.00±88.18/mm2)比较,其差异有统计学意义(P<0.05)。结论①成纤维细胞中GRP94的表达增高可能是增生性瘢痕发病机制之一;②抑制成纤维细胞GRP94的表达可能是激素治疗瘢痕增生的作用机制之一。

Objective To explore the role of GRP94 in the formation of hypertrophic sear by examining the expression of GRP94 in human hypertrophic sear tissue and the reaction of GRP94 to triamcinolone acetonide. Methods Hypertrophic scar tissues from 10 cases were collected as an experimental group for evaluating the expression of GRP94 by using immunohistochemistry staining and western blotting. Normal skin from other 10 other eases was used as a control group. The hyperophie scar model was established by transplanting human hypertrophic scar on to the back of nude mice, and subsequently treating it with triamcinolone acetonide or saline solution as a control. Resuits ① GRP94 protein was mainly expressed in keratinoeytes, fibroblasts, endothelial cells and inflammatory cells of both hypertrophic sear and normal skin tissues. Expression was primarily cytoplasmic, but there was also expression in a few nuclei. There was positive expression of GRP94 protein in hair follicles, sweat glands and sebaceous glands of the normal skin. ② The expression levels of GRP94 in epidermis between the experimental and control groups showed no significant difference （P 〉 0.05）, but expression in dermal fibroblasts was significantly different between these two groups （731.67 ± 148.31/mm^2, 202.00 ± 188.43/mm^2, P〈 0.05）. This result was further verified by the statistical data from western blotting （0.43 ± 0.25 in hypertrophic scar and 0.14 ± 0.03 in normal skin tissue, P 〈 0.05）. ③ Compared with the saline - treated hypertrophic sear tissues, numbers of positive fibroblasts in the dermis were significantly decreased after being treated with triamcinolone acetonide （from 485.00 ± 88.18/mm^2 to 247. 50 ± 81. 82/mm^2, P〈0.05）. Conclusion ① Overexpression of GRP94 in fibroblasts may play an important role in the formation and development of hypertrophic scar. ② Downregulation of GRP94 expression may be one of the mechanisms of action of glucocortieoid hormone treatment for hypertrophic scar.