负载槲皮素的羧甲基壳聚糖水凝胶促进糖尿病大鼠创面愈合  

Quercetin-loaded carboxymethyl chitosan hydrogel promotes wound healing in diabetic rats

作　　者：董美林 都海宇 刘源 Dong Meilin;Du Haiyu;Liu Yuan(Department of Burn and Plastic Surgery,The Second People’s Hospital of Lianyungang(Kangda College Affiliated Hospital of Nanjing Medical University),Lianyungang 222000,Jiangsu Province,China)

机构地区：[1]连云港市第二人民医院(南京医科大学康达学院附属医院)烧伤整形科,江苏省连云港市222000

出　　处：《中国组织工程研究》2025年第4期692-699,共8页Chinese Journal of Tissue Engineering Research

摘　　要：背景:槲皮素具有抗炎、抗癌、抗氧化、抗衰老、抗抑郁等药理作用,具有极高的药用价值。槲皮素可以促进正常大鼠创面的愈合,但是以槲皮素为主要成分的药物研发较少,限制了其在临床的广泛应用。目的:以水凝胶材料负载槲皮素,探讨槲皮素-羧甲基壳聚糖水凝胶在糖尿病大鼠创面中的应用效果。方法:①分别制备羧甲基壳聚糖水凝胶与槲皮素-羧甲基壳聚糖水凝胶,表征水凝胶的微观形貌、体外释药性能。②细胞实验:将小鼠L929成纤维细胞分4组培养,空白对照组常规培养,纯水凝胶组、药物组、载药水凝胶组分别加入羧甲基壳聚糖水凝胶、槲皮素溶液与槲皮素-羧甲基壳聚糖水凝胶,检测细胞增殖与迁移能力。③动物实验:取80只SD大鼠建立糖尿病模型,造模成功后在大鼠背部制作直径2 cm的全层皮肤缺损创面,随机分4组干预,空白对照组、纯水凝胶组、药物组、载药水凝胶组创面分别注射生理盐水、羧甲基壳聚糖水凝胶、槲皮素溶液、槲皮素-羧甲基壳聚糖水凝胶,每组20只,无菌纱布包扎固定。术后观察创面愈合情况、创面病理形态、炎症因子表达及血管生成情况。结果与结论:①扫描电镜下可见两种水凝胶的微观形貌相似,均呈疏松多孔的网络结构,并且槲皮素-羧甲基壳聚糖水凝胶具有良好的体外释药性能。②与空白对照组比较,其他3组细胞增殖与迁移率升高(P<0.05);载药水凝胶组细胞增殖与迁移率高于纯水凝胶组、药物组(P<0.05)。③载药水凝胶组大鼠术后5,11 d的创面愈合率高于其他3组;载药水凝胶组、纯水凝胶组、药物组大鼠术后18 d的创面愈合率基本达到100%,均高于空白对照组(P<0.05)。苏木精-伊红染色显示,载药水凝胶组大鼠术后18 d创面可见完整的皮肤与皮肤附属器,空白对照组、纯水凝胶组、药物组大鼠术后25 d创面可见完整的皮肤与皮肤附属器�BACKGROUND:Quercetin has anti-inflammatory,anti-cancer,anti-oxidation,anti-aging,anti-depression and other pharmacological effects,and has high medicinal value.Quercetin can promote wound healing in normal rats,but few drugs with quercetin as the main component have been developed,which limits its wide application in clinical practice.OBJECTIVE:To investigate the application effect of quercetin-carboxymethyl chitosan hydrogel on diabetic wound in rats by loading quercetin with hydrogel material.METHODS:(1)Carboxymethyl chitosan hydrogels and quercetin-carboxymethyl chitosan hydrogels were prepared respectively,and the micromorphology and in vitro drug release properties of the hydrogels were characterized.(2)Cell experiment:Mouse L929 fibroblasts were cultured in four groups.The blank control group was cultured conventionally.Carboxymethyl chitosan hydrogel,quercetin solution and quercetin-carboxymethyl chitosan hydrogel were added to pure hydrogel group,drug group,and drug-loaded hydrogel group,respectively,to detect cell proliferation and migration ability.(3)Animal experiments:Diabetic models were established in 80 SD rats.After successful modeling,full-layer skin defect wounds with a diameter of 2 cm were made on the back of rats,and these models were randomly divided into four groups.Normal saline,carboxymethyl chitosan hydrogel,quercetin solution,and quercetin-carboxymethyl chitosan hydrogel were injected into the wounds of blank control group,pure hydrogel group,drug group,and drug-loaded hydrogel group,respectively.Each group contained 20 animals,which were bound with sterile gauze.Wound healing,pathological morphology,expression of inflammatory factors,and angiogenesis were observed after operation.RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the microstructures of the two hydrogels were similar,both showed loose porous network structure,and quercetin-carboxymethyl chitosan hydrogels had good drug release performance in vitro.(2)Compared with blank control group,the cell proliferation and

关 键 词：创面愈合 槲皮素 敷料 水凝胶 糖尿病创面 羧甲基壳聚糖 皮肤创面 成纤维细胞 

分 类 号：R459.9[医药卫生—治疗学] R318.08[医药卫生—临床医学] R628