中药石香膏促进软组织缺损模型兔修复的机制
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摘要
背景:作者前期研究表明,在临床运用中药石香膏治疗大量的软组织缺损、慢性难愈合创面取得了患者认可的疗效。目的:探讨中药石香膏促进软组织缺损修复的机制。方法:成年雄性新西兰大白兔30只,由贵州医科大学实验动物中心提供,实验方案经贵阳中医学院动物实验伦理委员会批准。对30只大白兔采用经典的全层皮肤切割伤造模,随机分为石香膏组、阳性对照组(贝复济组)和空白对照组,分别在创面上外敷石香膏+用敷料覆盖、外喷重组牛碱性成纤维细胞生长因子+用敷料覆盖、不含药物的干净敷料覆盖创面。分别于造模后第3,6,9,12天进行换药,观察创面的愈合情况、肉芽组织情况,记录创面愈合时间;收集新生肉芽组织标本,病理切片观察成纤维细胞数量、血管改变情况;观察各组创面碱性成纤维细胞生长因子及转化生长因子β1蛋白表达。结果与结论:①石香膏组与贝复济组创面愈合率高,愈合时间短,疗效优于空白组;②病理学观察石香膏组可见明显毛细血管增生,炎症反应轻,新生肉芽中可见许多成纤维细胞及炎性细胞浸润;在同一取材的条件下,造模后6,12d,3组转化生长因子β1、碱性成纤维细胞生长因子蛋白表达均显著高于造模3d(P <0.05);③结果表明,石香膏增加创面内源性生长因子转化生长因子β1和碱性成纤维细胞生长因子表达量,促进软组织缺损修复。
BACKGROUND: Shixiang plaster has been shown to be effective for treating soft tissue defects and chronic healing.OBJECTIVE: To explore the mechanism of traditional Chinese medicine Shixiang plaster to promote the repair of soft tissue defects.METHODS: Thirty adult male rabbits were provided by Laboratory Animal Center of Guizhou Medical University, and the study was approved by the Experimental Animal Ethics Committee of Guiyang University of Traditional Chinese Medicine. All rabbits underwent classic full-thickness skin-cutting model, and then randomly divided into Shixiang plaster group(Shixiang plaster + dressing), Beifuji group(recombinant bovine basic fibroblast growth factor + dressing)and blank control group(dressing). Dressing change was performed at 3, 6, 9 and 12 days, respectively, and the wound healing and granulation tissue were observed, and the wound healing time was recorded. The specimens of newborn granulation tissue were collected to observe the number of fibroblasts and vascular changes by pathological section. The expression levels of basic fibroblast growth factor and transforming growth factor-β1 protein in wounds were detected.RESULTS AND CONCLUSION:(1) The wound healing rate in the Shixiang plaster and Beifuji group was high, the healing time was short,and the curative effect was better than that in the blank control group.(2) Pathological observation: Shixiang plaster group showed obvious capillary proliferation, mild inflammatory reaction, many fibroblasts and inflammatory cell infiltration in new granulation. The expression levels of transforming growth factor-β1 and basic fibroblast growth factor protein in wounds at 6 and 12 days after modeling under the same conditions in all groups were significantly higher than those at 3 days after modeling(P < 0.05).(3) These results suggest that Shixiang plaster can increase the expression levels of endogenous growth factors transforming growth factor-β1 and basic fibroblast growth factor in wounds and promote the repair of soft tissue defects.
BACKGROUND: Shixiang plaster has been shown to be effective for treating soft tissue defects and chronic healing.OBJECTIVE: To explore the mechanism of traditional Chinese medicine Shixiang plaster to promote the repair of soft tissue defects.METHODS: Thirty adult male rabbits were provided by Laboratory Animal Center of Guizhou Medical University, and the study was approved by the Experimental Animal Ethics Committee of Guiyang University of Traditional Chinese Medicine. All rabbits underwent classic full-thickness skin-cutting model, and then randomly divided into Shixiang plaster group(Shixiang plaster + dressing), Beifuji group(recombinant bovine basic fibroblast growth factor + dressing)and blank control group(dressing). Dressing change was performed at 3, 6, 9 and 12 days, respectively, and the wound healing and granulation tissue were observed, and the wound healing time was recorded. The specimens of newborn granulation tissue were collected to observe the number of fibroblasts and vascular changes by pathological section. The expression levels of basic fibroblast growth factor and transforming growth factor-β1 protein in wounds were detected.RESULTS AND CONCLUSION:(1) The wound healing rate in the Shixiang plaster and Beifuji group was high, the healing time was short,and the curative effect was better than that in the blank control group.(2) Pathological observation: Shixiang plaster group showed obvious capillary proliferation, mild inflammatory reaction, many fibroblasts and inflammatory cell infiltration in new granulation. The expression levels of transforming growth factor-β1 and basic fibroblast growth factor protein in wounds at 6 and 12 days after modeling under the same conditions in all groups were significantly higher than those at 3 days after modeling(P < 0.05).(3) These results suggest that Shixiang plaster can increase the expression levels of endogenous growth factors transforming growth factor-β1 and basic fibroblast growth factor in wounds and promote the repair of soft tissue defects.
引文
[1]付小兵,程天民,陆树良,等.中国人体表难愈合创面发生新特征与防治的创新理论与关键措施研究[Z].中国人民解放军总医院第一附属医院,中国人民解放军第三军医大学,上海交通大学医学院附属瑞金医院,温州医科大学,深圳普门科技有限公司,无锡市第三人民医院,中国人民解放军第三零六医院,上海交通大学医学院附属第九人民医院,苏州大学,中国人民解放军总医院.2015.
[2]费冀,陈久毅,张开伟,等.中药石香膏促进慢性难愈合创面修复的随机对照临床研究[J].辽宁中医杂志,2015,42(2):236-238.
[3]朱旭,陈久毅,王勇.中药促进指端缺如再生修复临床初探[J],内蒙古中医药,2012,31(1):50-50.
[4]费冀,陈久毅.中药“石香膏”促进糖尿病溃疡创面修复临床初探[J].亚太传统医药,2014,10(3):107-108.
[5]van Solingen C,Araldi E,Chamorro-Jorganes A,et al.Improved repair of dermal wounds in mice lacking microRNA-155.J Cell Mol Med,2014,18(6):1104-1112.
[6]邓步华.病理检验技术[M].北京:高等教育出版社,2005:77-81.
[7]Rawat S,Singh R,Thakur P,et al.Wound healing Agents from Medicinal Plants:A Review.Asian Pacific Journal of Tropical Biomedicine.2012;2(3):S1910-S1917.
[8]朱梦茹,郭澍,刘洋,等.脂肪来源干细胞外泌体在组织修复和再生医学中的研究进展[J].中国美容整形外科杂志,2018,29(12):757-760.
[9]高小月,张玉泉,杨晓清.人脐带间充质干细胞在组织损伤修复中的研究进展[J].生物医学工程与临床,2018,22(2):208-213.
[10]谢玉国,陈伟鹏,曾庆湖.旋髂浅动脉皮瓣修复手部皮肤软组织损伤中的治疗效[J].中国临床研究,2016,29(6):774-776.
[11]Eming SA,Martin P,Tomic-Canic M.Wound repair and regeneration:Mechanisms,signaling,and translation.Sci Transl Med.2014 Dec 3;6(265):265sr6.
[12]Reinke JM,Sorg H.Wound Repair and Regeneration.Eur Surg Res.2012;49(1):35-43.
[13]Velnar T,Ba T,Smrkolj V.The Wound Healing Process:An Overview of the Cellular and Molecular Mechanisms.J Int Med Res.2009;37(5):1528-1542.
[14]Buchanan PJ,Kung TA,Cederna PS.Evidence-based medicine:Wound closure.Plastic&Reconstructive Surgery.2014;134(6):1391-1404.
[15]Sonnemann KJ,Bement WM.Wound Repair:Toward Understanding and Integration of Single-Cell and Multicellular Wound Responses.Annu Rev Cell Dev Biol.2011;27:237-263.
[16]Thangapazham RL,Sharad S,Maheshwari RK.Phytochemicals in Wound Healing.Adv Wound Care(New Rochelle).2016;5(5):230-241.
[17]Barrientos S,Stojadinovic O,Golinko M S,et al.Growth factors and cytokines in wound healing.Wound Repair Regen.2008;16(5):585-601.
[18]Shi HX,Lin C,Lin BB,et al.The antiscar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo.PLoS One.2013;8(4):e59966.
[19]武姗,刘洋,朱旅云,等.转化生长因子β及其受体在糖尿病足创面愈合过程中作用机制的研究进展[J].中国糖尿病杂志,2017,25(6):569-572,
[20]周思政.皮肤创伤愈合和增生性瘢痕动物模型的研究进展[J].组织工程与重建外科杂志,2018,14(1):48-52.
[21]Yin H,Li XY,Hu SL,et al.IL-33 accelerates cutaneous wound healing involved in vedinupr upreguatlion ahernatively aivated macrophages.Molecular Immunology.2013;56:347353.
[22]刘公洪.湿性敷料治疗在烧伤创面的应用进展[J].西南军医,2012,14(1):113-114.
[23]武瑞仙,梁晨,王春晖,等.中医古籍中祛腐生肌方剂用药规律分析[J].辽宁中医杂志,2016,43(6):1146-1149.
[24]张晓芬,孙桂芳,陈亚峰,等.活血化瘀中药促进创面愈合的研究进展[J].光明中医,2015,30(8):1816-1820.
[25]聂元董,李刚.活血化瘀中药治疗足踝部软组织缺损皮瓣移植术后组织修复的临床研究[J].临床医药文献电子杂志,2016,3(51):10221.
[2]费冀,陈久毅,张开伟,等.中药石香膏促进慢性难愈合创面修复的随机对照临床研究[J].辽宁中医杂志,2015,42(2):236-238.
[3]朱旭,陈久毅,王勇.中药促进指端缺如再生修复临床初探[J],内蒙古中医药,2012,31(1):50-50.
[4]费冀,陈久毅.中药“石香膏”促进糖尿病溃疡创面修复临床初探[J].亚太传统医药,2014,10(3):107-108.
[5]van Solingen C,Araldi E,Chamorro-Jorganes A,et al.Improved repair of dermal wounds in mice lacking microRNA-155.J Cell Mol Med,2014,18(6):1104-1112.
[6]邓步华.病理检验技术[M].北京:高等教育出版社,2005:77-81.
[7]Rawat S,Singh R,Thakur P,et al.Wound healing Agents from Medicinal Plants:A Review.Asian Pacific Journal of Tropical Biomedicine.2012;2(3):S1910-S1917.
[8]朱梦茹,郭澍,刘洋,等.脂肪来源干细胞外泌体在组织修复和再生医学中的研究进展[J].中国美容整形外科杂志,2018,29(12):757-760.
[9]高小月,张玉泉,杨晓清.人脐带间充质干细胞在组织损伤修复中的研究进展[J].生物医学工程与临床,2018,22(2):208-213.
[10]谢玉国,陈伟鹏,曾庆湖.旋髂浅动脉皮瓣修复手部皮肤软组织损伤中的治疗效[J].中国临床研究,2016,29(6):774-776.
[11]Eming SA,Martin P,Tomic-Canic M.Wound repair and regeneration:Mechanisms,signaling,and translation.Sci Transl Med.2014 Dec 3;6(265):265sr6.
[12]Reinke JM,Sorg H.Wound Repair and Regeneration.Eur Surg Res.2012;49(1):35-43.
[13]Velnar T,Ba T,Smrkolj V.The Wound Healing Process:An Overview of the Cellular and Molecular Mechanisms.J Int Med Res.2009;37(5):1528-1542.
[14]Buchanan PJ,Kung TA,Cederna PS.Evidence-based medicine:Wound closure.Plastic&Reconstructive Surgery.2014;134(6):1391-1404.
[15]Sonnemann KJ,Bement WM.Wound Repair:Toward Understanding and Integration of Single-Cell and Multicellular Wound Responses.Annu Rev Cell Dev Biol.2011;27:237-263.
[16]Thangapazham RL,Sharad S,Maheshwari RK.Phytochemicals in Wound Healing.Adv Wound Care(New Rochelle).2016;5(5):230-241.
[17]Barrientos S,Stojadinovic O,Golinko M S,et al.Growth factors and cytokines in wound healing.Wound Repair Regen.2008;16(5):585-601.
[18]Shi HX,Lin C,Lin BB,et al.The antiscar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo.PLoS One.2013;8(4):e59966.
[19]武姗,刘洋,朱旅云,等.转化生长因子β及其受体在糖尿病足创面愈合过程中作用机制的研究进展[J].中国糖尿病杂志,2017,25(6):569-572,
[20]周思政.皮肤创伤愈合和增生性瘢痕动物模型的研究进展[J].组织工程与重建外科杂志,2018,14(1):48-52.
[21]Yin H,Li XY,Hu SL,et al.IL-33 accelerates cutaneous wound healing involved in vedinupr upreguatlion ahernatively aivated macrophages.Molecular Immunology.2013;56:347353.
[22]刘公洪.湿性敷料治疗在烧伤创面的应用进展[J].西南军医,2012,14(1):113-114.
[23]武瑞仙,梁晨,王春晖,等.中医古籍中祛腐生肌方剂用药规律分析[J].辽宁中医杂志,2016,43(6):1146-1149.
[24]张晓芬,孙桂芳,陈亚峰,等.活血化瘀中药促进创面愈合的研究进展[J].光明中医,2015,30(8):1816-1820.
[25]聂元董,李刚.活血化瘀中药治疗足踝部软组织缺损皮瓣移植术后组织修复的临床研究[J].临床医药文献电子杂志,2016,3(51):10221.