真皮细胞外基质水凝胶促进大鼠急性皮肤创面修复  

Dermal extracellular matrix hydrogel in promoting acute skin wound healing in rats

作　　者：董鸿斐 黄启林 杨熊 李帅 古瑞 孙红玉 汤礼军 Dong Hongfei;Huang Qilin;Yang Xiong;Li Shuai;Gu Rui;Sun Hongyu;Tang Lijun(Department of School of Clinical Medicine,Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of General Surgery&Pancreatic Injury and Repair Key Laboratory of Sichuan Province,General Hospital of Western Theater Command,Chengdu 610083,Sichuan Province,China)

机构地区：[1]西南医科大学临床医学院,四川省泸州市646000 [2]西部战区总医院全军普通外科中心,四川省胰腺损伤与修复重点实验室,四川省成都市610083

出　　处：《中国组织工程研究》2022年第10期1555-1560,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家临床重点专科军队建设项目(41732113),项目负责人:汤礼军;腹部创伤分级救治及器官功能修复系列研究(2019LH04),项目负责人:孙红玉。

摘　　要：背景:真皮细胞外基质(dermal extracellular matrix,d-ECM)已在临床创面修复中广泛使用,但真皮细胞外基质水凝胶(dermal extracellular matrix hydrogel,d-ECMH)是否可改善急性皮肤创面愈合目前尚缺乏相关研究。目的:探讨d-ECMH对大鼠急性皮肤创面的促愈合作用及机制。方法:将24只SD大鼠采用随机数字表法分为模型组、d-ECM组及d-ECMH组,每组8只。所有大鼠先建立全层皮肤缺损模型,模型组与d-ECMH组在创面与创缘分别注射PBS、d-ECMH,d-ECM组创面覆盖真皮细胞外基质,观察并评估创面愈合情况。14 d时处死所有大鼠,取其创面处皮肤组织进行苏木精-伊红染色、Masson染色、免疫组织化学染色及免疫荧光染色。实验获得西部战区总医院动物伦理委员会批准。结果与结论:①各组大鼠创面均随治疗时间延长而缩小,d-ECMH组术后14 d的创面愈合率与创面上皮化率高于d-ECM组、模型组(P<0.05),创面挛缩比率低于d-ECM组、模型组(P<0.05);②苏木精-伊红染色显示,相比模型组与d-ECM组,d-ECMH组皮肤创面修复更好,创面再上皮化程度更高,形成了新的皮肤附属器(如毛囊),真皮部分的基质更加整齐;③Masson染色显示,相比模型组与d-ECM组,d-ECMH组皮肤创面组织中胶原纤维明显增多且粗大;④免疫组化染色显示,d-ECMH组新生毛细血管数量多于模型组、d-ECM组(P<0.05),肿瘤坏死因子α与白细胞介素6含量低于模型组、d-ECM组(P<0.05);⑤免疫荧光染色显示,d-ECMH组新生创面内的M2型巨噬细胞数多于模型组及d-ECM组(P<0.05),M1型巨噬细胞数少于模型组、d-ECM组(P<0.05);⑥结果表明,d-ECMH可加速皮肤创面愈合,促进创面再上皮化,减轻创面挛缩,可能与促进创面内毛细血管新生与胶原纤维生成、减轻炎症、调控巨噬细胞向M2极化有关。BACKGROUND:Dermal extracellular matrix(d-ECM)has been widely used in clinical wound repair,but whether dermal extracellular matrix hydrogel(d-ECMH)can improve acute skin wound healing is still a lack of relevant research.OBJECTIVE:To explore the healing effect and mechanism of d-ECMH on acute skin wounds in rats.METHODS:Twenty-four SD rats were divided into model group,d-ECM group and d-ECMH group by random number table method,with 8 rats in each group.Firstly,all rats established a full-thickness skin defect model,and then the model group and d-ECMH group were immediately injected with equal volumes of PBS buffer and d-ECMH on the wound respectively after the operation,and the wound surface of the d-ECM group was covered with d-ECM to observe and evaluate wound healing.All rats were sacrificed on day 14,and the skin tissues of the wounds were subjected to hematoxylin-eosin staining,Masson staining,histoimmunochemistry and fluorescence staining.The experiment was approved by Animal Ethics Committee of General Hospital of Western Theater Command.RESULTS AND CONCLUSION:(1)The wound of rats in each group shrank with the prolongation of treatment time.Compared with the model group and the d-ECM group,the d-ECMH group had higher wound healing rate and wound surface skinization rate(P<0.05),and reduced wound contracture rate(P<0.05).(2)Hematoxylin-eosin staining showed that compared with the model group and the d-ECM group,the d-ECMH group had better skin wound repair and a higher degree of re-epithelialization of the wound,forming new skin appendages(such as hair follicles),and the matrix of dermis was more uniform.(3)Masson staining results showed that compared with the model and the d-ECM groups,the collagen fibers in the skin wound tissue were significantly increased and thicker in the d-ECMH group.(4)Immunohistochemical staining showed that the number of new capillaries in the skin wound tissue of the d-ECMH group was significantly more than that of the model group and d-ECM group(P<0.05).The contents of tumor nec

关 键 词：材料 细胞外基质 水凝胶 创面修复 巨噬细胞极化 皮肤 血管新生 

分 类 号：R459.4[医药卫生—治疗学] R318.08[医药卫生—临床医学]