基质金属蛋白酶-2及其组织抑制因子-2在糖尿病皮肤损伤修复过程中的动态变化

背景创面愈合是个复杂而有序的生物学过程,近期研究表明慢性刨面愈合延迟往往与一些特定的基质金属蛋白酶(matrix metalloproteinase,MMP)表达失调有关.目的研究活化的MMP(active matrlx metelloproteinase,aMMP)-2及其组织抑制因子(tissueinhibitor of metalloproteinases,TIMPs)在糖尿病皮肤损伤修复过程中的动态变化.设计随机对照实验研究.地点和对象实验在上海市第二医科大学附属瑞金医院烧伤研究所完成.对象为SPF级Sprague-Dawley大鼠72只,体质量250 g左右,雌雄不限,以链脲佐菌素(STZ)诱导的糖尿病大鼠深Ⅱ度烫伤为模型,将伤后0,1,3,7,21 d的组织标本进行组织块培养24 h.主要观察指标组织培养上清液中aMMP-2和TIMP-2的含量.结果伤后糖尿病和正常鼠皮肤组织释放的aMMP-2和TIMP-2逐渐升高,糖尿病组未损伤组织释放的aMMP-2明显高于正常组(t=3.214,P＜0.05),伤后21 d TIMP-2明显低于正常组(t=2.427,P＜0.05);正常组aMMP-2/TIMP-2比值基本稳定于一定的水平,而糖尿病组aMMP-2/TIMP-2比值逐渐下降,自伤后7 d起,显著低于0时相点(t=10 019,P＜0.01).结论糖尿病者在创伤前后皮肤组织中基质金属蛋白酶及其相关的生物活性物质的平衡均出现异常.

Changes of matrix metalloproteinase-2 and tissue inhibitor-2 of metalloproteinase in wound healing in diabetes

BACKGROUND: Wound healing is a complex and orderly biological process. Receut research shows that delayed chronic wound healing is always related to the expression disturbance of some specific matrix metalloproteinase (MMP).OBJECTIVE: To study the dynamic changes of activated MMP-2 and its tissue inhibitor (TIMP) in the process of wound healing in diabetes.DESIGN: A randomized controlled trial was conducted.SETTING and PARTICIPANTS: The experiment was done in the Institute of Burns, Ruijin Hospital, Shanghai Second Medical University. Seventy-two SPF grade SD rats provided by Shanghai Experimental Animal Centre of Chinese Academy of Medical Sciences were selected from both sex weighing 250 grams each.INTERVENTIONS: The diabetic rats induced by streptozotocin(STZ) with deep second degree burn were used as model. The tissue samples of 0, 1,3, 7, 21 postburn days were taken for tissue culture for 24 hours.MAIN OUTCOME MEASURES: The contents of MMP-2 and TIMP-2 in the supernatant solution of tissue culture.RESULTS: MMP-2 and TIMP-2 released from skin tissue of both wounded diabetic group and normal rats were gradually increased. The MMP-2 released from unwounded diabetic rats was much higher than that of normal group ( t = 3. 0214, P ＜ 0.05). TIMP-2 was much lower than that in control group in the 21st day after burn (t=2.427, P ＜0.05) .The ratio of MMP-2 to TIMP-2 was maintained at certain level. However, the ratio of diabetic group was gradually decreased and was much lower than that in the 0day (t=10.019, P ＜0.01).