血小板源伤口愈合因子促糖尿病大鼠伤口组织胶原合成机制的研究

目的 探讨外源性血小板源伤口愈合因子（PDWHF）促糖尿病大鼠伤口合成胶原与内源性转化生长因子-β（TGF-β1）基因表达的关系。方法 33只雄性SD大鼠，分为正常组（A组n＝9）、糖尿组（n＝24）。四氧嘧啶诱导糖尿病组大鼠血糖值大于1．8g/L1、2天后，在每组大鼠背部造成两块直径为1．8 cm的全层皮肤伤口。术后当天及以后连续6天，每天一次，糖尿病组大鼠一侧伤口局部应用PDWHF（100μg/伤口）作为治疗组（B组），另一侧伤口作为对照组（C组）。斑点杂交法测定伤后不同天数伤口组织中TGF－β1、Ⅰ型（α1）前胶原mRNA水平量。结果 伤后5、7天，B组伤口组织TGF－β1mRNA水平量是C组的4倍和5．6倍，经统计学处理有非常显著性差异（P＜0．01），但低于A组（P＜0．05）；伤后10天，三组间TGF-β1mRNA水平量无明显差异。伤后5、7天及10天，B组I型（α1）前胶原mRNA水平量明显高于C组，分别为2．1、1．8和2．3倍有非常显著性差异（P＜0．01）；但伤后5、7天仍明显低于A组（P＜0．05），伤后10天，两组间差异消失。结论 PDWHF促进糖尿病大鼠伤口内源性TGF－β1基因表达是其增强I型（α1）前胶原合成的重要原因。

STUDY ON THE MOLECULAR MECHANISMS INVOLVED IN THE INCREASED COLLAGEN SYNTHESIS BY PLATELET-DERIVED WOUND HEALING FACTORS DURING WOUND HEALING IN ALLOXAN-INDUCED DIABETIC RAT

OBJECTIVE: To explore the molecular mechanisms involved in the increased collagen synthesis by platelet-derived wound healing factors (PDWHF) during wound healing in alloxan-induced diabetic rats. METHODS: Thirty-three male SD rats were divided into two groups, the normal (n = 9) (group A) and the diabetic group (n = 24). Two pieces of full-thickness skin with diameter of 1.8 cm were removed from the dorsal site of diabetic rats. PDWHF (100 micrograms/wound) was topically applied to one side of the diabetic wounds (group B) on the operation day and then once a day in the next successive 6 days. Meanwhile, bovine serum albumin (100 micrograms/wound) was applied to the other side of diabetic wound as control group (group C) in the same way. Levels of transforming growth factor-beta 1 (TGF-beta 1) and procollagen I mRNA in wound tissue were inspected by dot blotting. RESULTS: TGF-beta 1 mRNA levels in group B were 4 folds and 5.6 folds compared with those in group C after 5 and 7 days (P < 0.01), however, still significantly lower than those of group A (P < 0.05). There was no significance difference among three groups on the 10th day after wounding. The levels for procollagen I mRNA in group B amounted to 2.1, 1.8 and 2.3 folds of those in group C after 5, 7, and 10 days (P < 0.01), respectively. Compared with those in the group A, procollagen I mRNA levels in the group B were significantly lower after 5 and 7 days (P < 0.05), and no significant difference was observed between group B and A after 10 days. CONCLUSION: One important way for PDWHF to enhance the collagen synthesis in diabetic wound healing is to increase the gene expression of endogenous TGF-beta 1.