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MEBT/MEBO通过mTORC信号通路对慢性难愈合创面MMP-3、MMP-8表达水平的影响
Effect of MEBT/MEBO on the Expression of MMP-3 and MMP-8 in Chronic Refractory Wounds Via mTORC Signaling Pathway

唐习强,韦骋,王雪玲,包崇婵,田馨如,葛星月,唐乾利.MEBT/MEBO通过mTORC信号通路对慢性难愈合创面MMP-3、MMP-8表达水平的影响[J].中国烧伤创疡杂志,2022,(2):77~84.

DOI：

中文关键词: 皮肤再生医疗技术湿润烧伤膏慢性难愈合创面哺乳动物雷帕霉素靶蛋白复合物信号通路基质金属蛋白酶

英文关键词:Skin regenerative medical technology MEBO Chronic refractory wound Mammalian target of rapam-ycin complex（mTORC） Signaling pathway Matrix metalloproteinase

基金项目:国家自然科学基金面上项目(81774327)；广西自然科学基金项目(2017GXNSFAA198321)；“广西特聘专家”专项经费资助项目(桂人才通字[2019] 13 号)；广西医学高层次领军人才培养“139”计划资助项目(桂卫科教发 [2018] 22号)

作者	单位
唐习强	533000 广西百色, 右江民族医学院/桂西高发病防治重点实验室；533000 广西百色，右江民族医学院附属医院心胸外科
韦骋	533000 广西百色, 右江民族医学院/桂西高发病防治重点实验室
王雪玲	530001 广西南宁，广西中医药大学研究生院2019 级中医外科专业
包崇婵	533000 广西百色, 右江民族医学院/桂西高发病防治重点实验室
田馨如	533000 广西百色, 右江民族医学院/桂西高发病防治重点实验室
葛星月	533000 广西百色, 右江民族医学院/桂西高发病防治重点实验室
唐乾利	533000 广西百色, 右江民族医学院/桂西高发病防治重点实验室

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中文摘要:

【摘要】目的探究分析皮肤再生医疗技术（MEBT/MEBO）通过哺乳动物雷帕霉素靶蛋白复合物（mTORC）信号通路对慢性难愈合创面组织中基质金属蛋白酶-3（MMP-3）、基质金属蛋白酶-8（MMP-8）表达水平的影响。方法选取SPF级雄性Wistar大鼠60只适应性饲养7 d后，按照随机数表法将其随机分为空白组、对照组、模型组、rb-bFGF组、MEBO组，每组12只，其中空白组大鼠只做备皮处理，对照组大鼠于脊柱两侧建立急性创面模型，模型组、rb-bFGF组、MEBO组大鼠于脊柱两侧建立慢性难愈合创面模型；模型建立后，空白组大鼠备皮处皮肤及对照组、模型组大鼠创面予以生理盐水纱布换药处理；rb-bFGF组大鼠创面予以rb-bFGF换药处理，MEBO组大鼠创面予以MEBO换药处理，对比观察各组大鼠干预第3、7、14天时创面愈合率以及皮肤/创面组织中MMP-3、MMP-8、p-mTORC蛋白及相应mRNA的表达水平。结果干预第7、14天，对照组、rb-bFGF组、MEBO组创面愈合率均高于模型组（P均＜0.05）。干预第3、7、14天，对照组、rb-bFGF组、MEBO组大鼠创面组织中MMP-3、MMP-8、p-mTORC蛋白及MMP-3、MMP-8表达水平均呈先升高后降低的趋势，而模型组呈持续升高的趋势；干预第3、7-天，rb-bFGF组和MEBO 组大鼠创面组织中MMP-3、MMP-8、p-mTORC蛋白及MMP-3、MMP-8 mRNA表达水平均明显高于模型组（P均＜0.05），而干预第14天，rb-bFGF组和MEBO组大鼠创面组织中MMP-3、MMP-8、p-mTORC蛋白及MMP-3、MMP-8 mRNA表达水平均明显低于模型组（P均＜0.05），且干预第3、7天rb-bFGF组大鼠创面组织中MMP-3?MMP-8蛋白表达水平均明显低于MEBO组（P均＜0.05），而干预第3、7、14天两组大鼠创面组织中MMP-3?MMP-8 mRNA 表达水平均无明显差异（P均＞0.05）；干预第3、7、14 天，各组大鼠创面组织中mTORC mRNA表达水平均无明显变化（P均＞0.05）。结论 MEBT/MEBO可通过调控mTORC信号通路中MMP-3和MMP-8的表达水平，促进慢性难愈合创面愈合。

英文摘要:

【Abstract】 Objective To investigate the effect of the skin regenerative medical technology (MEBT/ MEBO) on the expression of matrix metalloproteinase-3 (MMP-3and matrix metalloproteinase-9 (MMP-9) in chronic refractory wounds via mammalian target of rapamycin complex (mTORC) signaling pathway. Methods 60 SPF-bred male Wistar rats were selected and, after adaptive feeding for seven days, randomized into blank group, control group, model group,rb-bFGF group and MEBO group using the random number table, 12 rats in each group. In blank group, only skin preparation was done, while acute wound models were made on both sides of the spine of rats in control group, and chronic refractory wound models were established on both sides of the spine of rats respectively in model group, rb-bFGF group and MEBO group. After model establishment, the prepared skin in blank group and the wounds in control group and model group were managed with dressing change of normal saline gauzes, and the wounds in rb-bFGF group and MEBO group were respectively managed with dressing change of recombinant bovine basic fibroblast growth factor (rb-bFGF) and MEBO. The wound healing rate, expression levels of MMP-3, MMP-8, p-mTORC and their corresponding mRNA in skin or wound tissues on day 3, 7 and 14 of interventions were observed and compared among the five groups. Results The wound healing rates in control group, rb-bFGF group and MEBO group on day 7 and 14 of interventions were all significantly higher than model group (all P<0.05). On day 3, 7 and 14 of interventions, the expression lelves of MMP-3, MMP-8, p-mTORC, and mRNA of MMP-3 and MMP-8 in wound tissues in control group, rb-bFGF group and MEBO group all showed a trend of increase followed by decrease, whereas that in model group showed a continuously increasing trend. On day 3 and 7 of interventions, the expression levels of MMP-3, MMP-8, p-mTORC, and mRNA of MMP-3and MMP-8 in wound tissues in rb-bFGF group and MEBO group were all markedly higher than model group (all P＜0.05), whereas the levels of theseitems in rb-bFGF group and MEBO group on day 14 of interventions were obviously lower than model group (all P <0.05). The expression levels of MMP-3 and MMP-8in rb-bFGF group were markedly lower than MEBO group respectively on day 3 and 7 of interventions (all P＜0.05), while no significant difference was observed between rb-bFGF group and MEBO group in terms of expression levels of mRNA of MMP-3and MMP-8 respectively on day 3, 7 and 14 of interventions (all P＞0.05). Respectively on day 3, 7 and 14 of interventions, the expression of mTORC mRNA presented no significant differences among the five groups (all P＞0.05).Conclusion MEBT/-MEBO can promote the healing of chronic refractory wounds by regulating the expression of MMP-3 and MMP-8 in wound tissues via mTORC signaling pathway.