课题背景：碱性成纤维细胞生长因子能诱导微血管的形成、增殖、分化，促进毛细血管内皮细胞及血管周围的细胞增殖，从而加速创面愈合。壳多糖在抗菌、消炎、降血糖、止血以及抗肿瘤等方面都发挥着生物活性作用。两者促进创面愈合作用机制存在互补性，为两者的联合应用提供了依据。

创新要点：实验应用利用基因重组技术制备的外源性成纤维细胞生长因子，其结构和生物学活性与人体内源性成纤维细胞生长因子高度一致。尝试将其与壳多糖联合应用，增加了其与创面接触的时间和面积，使其处于缓释状态，更有助于促进创面愈合。

相关链接：碱性成纤维细胞生长因子可促进各种组织损伤尤其是难愈合创面和大面积烧伤创面的修复。壳多糖对多种细菌的生长具有抑制作用。已有研究表明壳多糖可使表皮生长因子处于缓释状态，使其最大限度的发挥功效，协同促进伤口愈合。但如何更好地发挥碱性成纤维细胞生长因子的药理作用，还有待于进一步的深入研究。


摘要
目的：壳多糖具有抗菌消炎和收敛作用。碱性成纤维细胞生长因子具有促进血管生成、促进神经生长等功能，是创伤愈合和上皮形成的重要调节物。实验联合应用壳多糖和碱性成纤维细胞生长因子，观察其对创面愈合的影响。
方法：实验于2006-04/2007-01在河北省人民医院实验室及河北医科大学第四附属医院实验室完成。实验室标准均为生物安全二级(BSL-2)。①实验材料：48只雄性健康Wistar大鼠由河北医科大学实验动物中心提供，体质量200~250 g，清洁级，实验过程中对动物处置符合动物伦理学标准。②实验方法：以切割法制备大鼠创伤模型，造成全层皮肤创面。将48只Wistar大鼠随机分为对照组、壳多糖组、生长因子组、壳多糖+生长因子组,并分别给予蒸馏水、100 g/L壳多糖、1 000 IU/mL碱性成纤维细胞生长因子、100 g/L壳多糖+1 000 IU/mL碱性成纤维细胞生长因子药液治疗，每组12只。③实验评估：以创面愈合时间和速率、新生毛细血管、炎症细胞和细胞渗出的变化以及血管内皮生长因子在创面组织中的表达来评价修复效果。
结果： 48只大鼠全部进入结果分析。①壳多糖+生长因子组创面愈合时间最快（P < 0.01）。②与其他3组比较，壳多糖+生长因子组第3天有较多毛细血管生成，第14天成纤维细胞排列整齐。③壳多糖+生长因子组血管内皮生长因子表达在术后第10天达到最高峰，至伤后第14天仍保持高水平，且明显高于其他3组（P < 0.01）。
结论：壳多糖+碱性成纤维细胞生长因子促进伤口愈合，缩短愈合过程，提高愈合质量，两者联合应用可更大限度发挥各自功效。
关键词：创伤愈合；动物创伤模型；壳多糖；碱性成纤维细胞生长因子；血管内皮生长因子

仇树林，冯敏，张培培，赵伟，朱昊.壳多糖与外源性碱性成纤维细胞生长因子联合应用修复创面愈合的评估 [J].中国组织工程研究与临床康复，2008，12(10):1823-1826 [www.zglckf.com/zglckf/ejournal/upfiles/08-10/10k-1823(ps).pdf]

Influence of chitosan and basic fibroblast growth factor on wound healing

Abstract

AIM：Chitosan can resiste bacteria, and eliminate inflammation and astriction. Basic fibroblast growth factor (bFGF) can promote angiogenesis and accelerate nerve growth, which has been recognized as an important modifier in the process of wound healing and epithelization. This study observed the effects of chitosan mixed with bFGF on wound healing.
METHODS: The experiment was performed in the Clinical Medical Research Center of Hebei Provincial People's Hospital and the Fourth Hospital of Hebei Medical University between April 2006 and January 2007. Both laboratories were of Class Ⅱ Biosafety. ①Forty-eight healthy male adult Wistar rats of clean grade and 200-250 g were provided by the Experimental Animal Center of Hebei Medical University. Treatment of animals was accroded with Animal Ethics standards.②Rat full-thickness dermal wounds model was set up by cutting method. Forty-eight Wistar rats were randomly divided into control group, chitosan group, bFGF group, and chitosan + bFGF group (n =12), and treated with distilled water, 100 g/L chitosan, 1 000 IU/mL bFGF, and 100 g/L chitosan + 1 000 IU/mL bFGF, respectively. ③The wound healing time and rate, the changes in new capillary vessel, inflammatory cells and cell infiltration, and the expression of vascular endothelial growth factor (VEGF) were used to evaluate the repair effects.
RESULTS: All 48 rats were involved in the result analysis. ①The healing rate of chitosan + bFGF group was the fastest (P < 0.01). ②chitosan +bFGF group showed more angiogenesis at the 3rd day compared with the others, and the fibroblasts arranged orderly at the 14th day. ③The expression of VEGF in chitosan +bFGF group achieved peak on day 10 and maintained a high level until day 14, which was obviously higher than the others (P < 0.01).
CONCLUSION: Chitosan and bFGF can promote and accelerate wound healing, and enhance the qualities of wound healing. The combination of chitosan and bFGF can maximize each efficiency.

Qiu SL, Feng M, Zhang PP, Zhao W, Zhu H.Influence of chitosan and basic fibroblast growth factor on wound healing.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(10):1823-1826(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-10/10k-1823(ps).pdf]