| 李杰辉,卢 维,刘雪琴,陈壮丽.MEBO对糖尿病溃疡大鼠创面组织中MMP-9、MMP-2、TIMP-1、TIMP-2动态表达的影响[J].中国烧伤创疡杂志,2021,(1):1~7. |
| DOI： |
| 中文关键词: 湿润烧伤膏 糖尿病溃疡 基质金属蛋白酶 基质金属蛋白酶抑制剂 胶原蛋白 |
| 英文关键词:MEBO Diabetic ulcer Matrix metalloproteinase Tissue inhibitor of metalloproteinase Collagen |
| 基金项目:国家自然科学基金（81660793） |
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| 中文摘要: |
| 目的 探讨分析湿润烧伤膏（MEBO）对糖尿病溃疡大鼠创面组织中基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶抑制剂-1（TIMP-1）及基质金属蛋白酶抑制剂-2（TIMP-2）表达水平的影响。方法 从160只健康雄性SD大鼠中随机选取120只制备大鼠糖尿病模型，其余40只正常喂养；最终选取90只造模成功大鼠随机分为模型组、MEBO组与bFGF组，每组30只，与此同时随机选取未予特殊处理的30只大鼠作为空白组，所有大鼠均做全层皮肤缺损创面，空白组与模型组大鼠创面予以凡士林油纱换药处理、MEBO组大鼠创面予以MEBO药纱换药处理、bFGF组大鼠创面予以重组牛碱性成纤维细胞生长因子（rb-bFGF）药纱换药处理，对比观察各组大鼠干预第4、6、12天时创面愈合率以及MMP-9、MMP-2、TIMP-1、TIMP-2与胶原蛋白水平变化情况。结果 （1）干预第4、6、12天，模型组大鼠创面愈合率均明显低于其他各组（P均＜0.05），空白组大鼠创面愈合率均明显高于其他各组（P均＜0.05），而MEBO组与bFGF组间无明显差异（P均＞0.05）。（2）干预第4、6、12天，模型组大鼠创面组织中MMP-9及MMP-2 mRNA表达水平均明显高于其他各组（P均＜0.05），TIMP-1及TIMP-2 mRNA表达水平均明显低于其他各组（P均＜0.05）；除干预第6天MEBO组大鼠创面组织中TIMP-1 mRNA表达水平明显高于bFGF组（P＜0.05）外，其余各时间点MEBO组与bFGF组大鼠创面组织中MMP-9、MMP-2、TIMP-1及TIMP-2 mRNA表达水平均无明显差异（P均＞0.05）。（3）干预第4、6、12天，模型组大鼠创面组织中胶原蛋白水平明显低于其他各组（P均＜0.05）；除干预第4天MEBO组大鼠创面组织中胶原蛋白水平明显高于bFGF组（P＜0.05）外，其余各时间点MEBO组与bFGF组大鼠创面组织中胶原蛋白水平均无明显差异（P均＞0.05）。结论 MEBO可通过调控糖尿病溃疡大鼠创面组织中MMP-9、MMP-2、TIMP-1、TIMP-2的表达水平改善胶原蛋白过度降解，维持细胞外基质代谢平衡，进而促进创面愈合，调节MMP-9/TIMP-1、MMP-2/TIMP-2的比例失衡可能是其促进糖尿病溃疡创面愈合的作用靶点。 |
| 英文摘要: |
| 【Abstract】Objective To investigate the effect of MEBO on the expression levels of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the wound tissues of rats with diabetic ulcers. Methods Of 160 healthy male SD rats, 120 were randomly selected to make rat models of diabetes and the remaining 40 were fed normally. At the end, 90 rats with established diabetic models were selected and randomly divided into a model group, a MEBO group and a bFGF group, with 30 rats in each group, and the other 30 rats randomly selected from the normally-fed 40 rats without special treatment were set as a blank group. Full-thickness skin defect wounds were made on all rats. The wounds in the blank group and model group were treated with Vaseline-impregnated gauze dressing, and the wounds in the MEBO group were treated with MEBO-impregnated gauze dressing, and the wounds in the bFGF group were treated with recombinant bovine basic fibroblast growth factor (rb-bFGF)-impregnated gauze dressing. The wound healing rate and changes of levels of MMP-9, MMP-2, TIMP-1, TIMP-2 and collagen were compared between the two groups on day 4, 6 and 12 of treatment. Results (1) On day 4, 6 and 12 of treatment, the wound healing rates in the model group were significantly lower than that in the other three groups (all P<0.05), the wound healing rates in the blank group were markedly higher than that in the other groups (all P <0.05), while no significant difference was observed between MEBO group and bFGF group (all P>0.05). (2) On day 4, 6 and 12 of treatment, in the model group the expression levels of MMP-9 and MMP-2 mRNA in the wound tissues of rats were significantly higher than that in the other groups (all P＜0.05), and the expression levels of TIMP-1 and TIMP-2 mRNA in the wound tissue of rats were obviously lower than that in the other groups (all P<0.05). On day 6 of treatment, the expression level of TIMP-1 mRNA in the wound tissue of rats in the MEBO group was significantly higher than that in the bFGF group (P<0.05), apart from this, no significant difference was observed in the expression levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 mRNA in the wound tissues of rats between MEBO group and bFGF group at the other time points (all P>0.05). (3) On day 4, 6 and 12 of treatment, the collagen level in the wound tissues of rats in the model group was significantly lower than that in the other groups (all P<0.05). No significant difference was observed between MEBO group and bFGF group in terms of collagen level at the three time points (all P>0.05), except on day 4 of treatment the collagen level in the wound tissue of rats in MEBO group being significantly higher than that in the bFGF group (P<0.05). Conclusion MEBO can slow down the over-degradation of collagen by regulating the expression levels of MMP-9, MMP-2, TIMP-1, TIMP-2 in the wound tissues of rats with diabetic ulcers, maintain the metabolic balance of extracellular matrix and further promote wound healing. Maintaining a balance between MMP-9/TIMP-1 and MMP-2/TIMP-2 may be the target of MEBO in promoting the wound healing of diabetic ulcer. |
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