碱性成纤维细胞生长因子与鸦胆子乳膏联合应用对兔背创伤愈合的修复作用(英文)

Effect of basic fibroblast growth factor plus Brucea Javanica oil emulsion on repairing back skin wound of rabbits

背景:有实验证明将碱性成纤维细胞生长因子和鸦胆子乳膏联合应用能促进创伤愈合并抑制瘢痕形成。目的:观察碱性成纤维细胞生长因子与鸦胆子油乳剂联用对兔兔背部刀割伤的促愈合作用。设计:随机对照观察。单位:暨南大学医药生物技术研究开发中心,暨南大学药学院。材料:实验于2005-06/09在暨南大学药学院完成。选用8只北京产大耳白兔,雌雄各半,体质量2.0～2.5kg,由南方医科大学实验动物中心提供。碱性成纤维细胞生长因子无菌冻干粉制剂(广州长生基因药业有限公司,批号:20040219),临用前用注射用水配制成溶液。鸦胆子乳剂由沈阳药科大学药剂研究室姚崇舜教授提供(浙江三九邦而康药业有限公司,批号:20040206)。方法:将实验兔麻醉消毒,背中部脊柱两侧各旁开1.5cm处,由前至后共切割5个圆形创面,直径1.8cm,面积2.54cm2,抽签法随机将每只实验兔的5个创面分为碱性成纤维细胞生长因子治疗组(碱性成纤维细胞生长因子用量为90 U/cm2)、综合治疗组(碱性成纤维细胞生长因子用量为90U/cm2,30min后涂抹鸦胆子乳膏30mg/cm2)、鸦胆子乳治疗组(涂抹鸦胆子乳膏30mg/cm2)、空白基质组(空白基质30mg/cm2)及空白对照组(涂抹生理盐水)。伤后即开始用药,以后每天换药1次,至伤后第16天。术后用透明膜描记法(用洁净保鲜膜覆盖伤口,描出创面大小,剪下称重,换算成面积计算)记录伤后第4,8,12,16天创面面积;用注水法测量伤腔容积;伤后第8,16天取创面组织,经常规组织切片染色后观察创面肉芽组织生长与再上皮化情况。主要观察指标:各组实验兔伤后不同时间点创面面积、伤腔容积及创面肉芽组织生长与再上皮化情况。结果:纳入实验兔8只全部进入结果分析。①各组实验兔不同时间点创面面积:综合治疗组用药后4,8,12d创面面积分别为(2.05±0.35),(1.59±0.25),(0.55±0.25)cm2,小于空白对照组相应时间点[(2.53±0.30),(2.41±0.19),(1.09±0.34)cm2,P<0.05～0.01]。碱性成纤维细胞生长因子治疗组用药后8,12d创面面积分别为(1.71±0.31),(0.51±0.10)cm2,小于空白对照组相应时间点(P<0.05～0.01)。②各组实验兔伤腔容积:碱性成纤维细胞生长因子治疗组实验兔伤后4d创面体积为(0.49±0.12)mL,小于空白对照组相应时间点[(0.59±0.1)mL,P<0.05],综合治疗组伤后4,8d创面体积分别为(0.47±0.12),(0.30±0.08)mL,小于空白对照组相应时间点[(0.59±0.1),(0.41±0.07)mL,P<0.05,0.01]。③各组实验兔创面组织肉芽组织生长与再上皮化情况:综合治疗组伤后8d显示炎症反应较轻,成纤维细胞增生显著,其毛细血管胚芽与成纤维细胞数量多于空白对照组;模型组与空白基质组情况基本相同,炎症反应重,肉芽组织增加不明显,新生毛细血管少,表皮细胞增殖不明显。伤后16天,综合治疗组的创面收缩与再上皮化明显,新生上皮向创面中心爬行较快。结论:鸦胆子乳剂及碱性成纤维细胞生长因子联合应用对兔背部刀伤创面有明显的促修复作用。

BACKGROUND： It has been proved that the application of basic fibroblast growth factor Javanica oil emulsfon can accelerate wound healing and inhibit scar formation. OBJECTIVE： To observe the effects of bFGF plus Brucea Javanica oil emulsion cream on accelerating the skin wound healing of rabbfts. DESIGN ： A randomized controlled observation SETTING： Center of Biotechnological Research and Development. Jinan University; College of Pharmacy, Jinan University MATERIALS：The experiment was carried out in the College of Pharmacy, Jinan University from June to September in 2004, Eight Beijing big-ear white rabbits （4 males and 4 females） of 2.0-2.5 kg were provided by the experimental anima center of Southern Medical University （certification number： SoKx-2002-010）. bFGF sterile freeze dried powder agent, provided by Guangzhou Changsheng Gene Pharmaceutical Co.,Ltd （batch number： 20040219; specific activity was 6 000 U/bottle）, was prepared to solution with water for injection before application. Brucea Javanica oil emulsion （manufactured by Zhejiang 999 Bang＇erkang Pharmaceutical Co,,Ltd,） was provided by Professor Yao from staff Room of Phar. macy, Shenyang Pharmaceutical University. METHODS： The rabbits were anesthetized and disinfected, 5 round wounds with diameter of 1.8 cm and area of 2.54 cm^2 were induced from front to back by bilateral incision at 1.5 cm from middle spine of rabbit, The 5 wounds of each rabbit were randomly divided into bFGF-treated group （90 U/cm^2）, bFGF＋Brucea Javanica oil emulsion group [the wound was smeared with Brucea Javanica oil emulsion （30 mg/cm^2） 30 minutes after bFGF （90 U/cm^2）], Brucea Javanica oil emul- sion treated group [the wound was smeared with Brucea Javanica oil emulsion （30 mg/cm^2）], blank emulsion group （30 mg/cm^2） and blank control group （the wound was smeared with saline）. The medication was give immediately after injury, and changed once aday for 16 days, At 4, 8, 12 and 16 days after injury, the wound areas were recorded with the method of hyaline membrane tracing （the wound was covered with clean saran wrap, the size of wound was traced, and then sheared to be weighed, and converted to calculate, the area）, and the volume of wounded cavity was measured by infusing water. At 8 and 16 days, the wound tissue was removed, stained after routine tissue sections, and the conditions of growth of granulation tissue and reepithelization on the wound surface were observed. MAIN OUTCOME MEASURE ： The wound area, volume of wounded cavity, and the conditions of growth of granulation tissue and reapithelization on the wound surface were obviously at different time points after injury in each group. RESULTS：All the 8 rabbits were involved in the analysis of results. ① Wound areas at different time points in each group： The wound areas in the bFGF＋Brucea Javanica oil emulsion group at 4, 8 and 12 days after medication were smaller than those in the blank control group at corresponding time points [（2,05±0.35）, （1.59±0.25）, （0.55±0.25） cm^2; （2.53±0.30）, （2.41±0.19）. （1.09±0.34） cm^2, P 〈 0.05-0.01]. The wound areas in the bFGF group at 8 and 12 days after medication were （1.71±0.31） and （0.51±0.10） cm^2, which were significantly smaller than those in the blank control group at corresponding time points （P 〈 0.05-0.01）, ② Volume of the wounded cavity in each group： The wound volume in the bFGI= group at 4 days after injury was markedly smaller than that in the blank control group at corresponding time point [（0.49±0.12）, （0.59±0.1） mL, P 〈 0.05]. The wound volumes in the bFGF＋Brucea Javanica oil emulsion group at 4 and 8 days after injury were significantly smaller than those in the blank control group at corresponding time points [（0.47± 0.12）, （0.30±0.08） mL; （0.59±0.1）, （0.41±0.07） mL, P 〈 0.05, 0.01].③ Growth of granulation tissue and reeplthelization on the wound surface in each group： At 8 days after injury, the inflammatory reaction was milder and fibroblasts proliferated significantly in the bFGF＋Brucea Javanica oil emulsion group, and the numbers of capillary plumules and fibroblasts were signlficanUy more than those in the blank control group. The conditions in the blank control group and blank emulsion group were generally the same that there were severe inflammatory reactions, obvious increase of granulation tissue, fewer new capillaries, and unobvious proliferation of epidermic ceils. At 16 days after injury, the contraction and reepithelization on the wound surface were obvious, and the new epithelia went towards the wound center rapidly in the bFGF＋Brucea Javanica oil emulsion group. CONCLUSION： The application of Brucea Javanica oil emulsion plus bFGF can obviously accelerate the repair of incised wound on the back of rabbits.