积雪草苷对增生性瘢痕中转化生长因子-βmRNA及基质金属蛋白酶类表达的影响

目的探讨积雪草苷对人增生性瘢痕中转化生长因子β（TGF-β）mRNA和基质金属蛋白酶及其组织抑制剂（MMPS／TIMPS）表达的影响。方法临床上收集烧伤后5～8个月经积雪草苷治疗和非积雪草苷治疗的增生性瘢痕标本各9例。采用原位杂交和免疫组织化学方法，分别检测增生性瘢痕中TGF-β1 mRNA、TGF-β2 mRNA、TGF-β3 mRNA及MMP1、MMP2、TIMP1、TIMP2和Ⅰ、Ⅲ型胶原的表达水平，并利用图象分析方法进行结果分析。结果TGF-β mRNA在增生性瘢痕中主要表达于成纤维细胞胞质，经积雪草苷治疗的增生性瘢痕中TGF-β1 mRNA表达明显减少，胞质淡染，统计学上与非积雪草苷治疗组TGF-β1 mRNA表达有显著性差异（P〈0．01）；而TGF-β1，mRNA在积雪草苷治疗的增生性瘢痕中表达增多，明显高于非积雪草苷治疗组的TGF-β1 mRNA表达（P〈0．05）。MMPS／TIMPS在增生性瘢痕中也表达于成纤维细胞胞质，经积雪草苷治疗的增生性瘢痕中TIMP1。表达明显减少，与非积雪草苷治疗组TIMP1表达有显著性差异（P〈0．01）；而MMP1、MM2,及TIMP2在上述两组中表达无显著性差异（P〉0．05）。Ⅰ、Ⅲ型胶原在增生性瘢痕中表达．经积雪草苷治疗的增生性瘢痕中Ⅰ型胶原排列整齐，含量较少，与非积雪草苷治疗组有显著差异（P〈0．05）；而Ⅲ型胶原在两组增生性瘢痕中表达无显著性差异（P〉0．05）。结论积雪草苷通过降低TGF-β1 mRNA表达和增加TGF-β3 mRNA的表达，引起TIMP1表达明显减少，从而MMP1／TIMP1相对比例增加，达到促进Ⅰ型胶原降解，减轻瘢痕增生的作用。

Effect of asiaticoside on the expression of transforming growth factor-beta mRNA and matrix metalloproteinases in hypertrophic scars

OBJECTIVE: To investigate the effect of asiaticoside on the expressions of transforming growth factor (TGF)-beta mRNA, matrix metalloproteinases (MMPS) and tissue inhibitors of metalloproteinases (TIMPs) in postburn hypertrophic scars. METHODS: Nine specimens of postburn (5-8 months) hypertrophic scars with asiaticoside treatment and 9 without asiaticoside treatment were collected for testing the expressions of MMPS, TIMPs, type I and III collagen and TGF-beta mRNA by immunohistochemistry and in situ hybridization methods, followed by image analysis of the results. RESULTS: The expressions of TGF-beta mRNA and MMPS/TIMPS were all detected in the fibroblast cytoplasm. The expression of TGF-beta(1) mRNA in asiaticoside-treated scars was significantly lower than that in scars without asiaticoside treatment (P<0.01). In contrast, the expression of TGF-beta(3) mRNA was significantly higher in asiaticoside group (P<0.05). The expression of TIMP1 in asiaticoside group was significantly lower than that in non-asiaticoside group (P<0.01), and the expression of type I collagen in asiaticoside-treated scars was lower than that in non-asiaticoside-treated specimens (P<0.05), but the expression of MMP(1), MMP(2) and TIMP(2) and type III collagen exhibited no significant differences between the two groups (P>0.05). CONCLUSION: Asiaticoside can down-regulate TGF-beta(1) mRNA and TIMP(1) expressions and up-regulate TGF-beta(3) mRNA expression in postburn hypertrophic scars, and is also capable of decomposing the products of type I collagen, contributing to the reduction of hypertrophic scar formation.