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中华损伤与修复杂志(电子版)

中华损伤与修复杂志(电子版) ›› 2019, Vol. 14 ›› Issue (05) : 355 -360. doi: 10.3877/cma.j.issn.1673-9450.2019.05.007

所属专题： 文献；

论著

基质细胞衍生因子-1α联合Integra支架修复全层皮肤缺损创面的实验研究
高建廷1, 林剑彪1, 刘国浚1, 朱聪1, 吴本文1, 丁真奇1, 黄国锋1,†()   
  1. 1. 363000　漳州，解放军联勤保障部队第九零九医院　厦门大学附属东南医院骨科
  • 收稿日期:2019-07-25 出版日期:2019-10-01
  • 通信作者: 黄国锋
  • 基金资助:
    福建省自然科学基金(2016J05208); 军队后勤科研项目(CNJ16C013); 军队医学科技青年培育项目(19QNP046)

Stromal cell-derived factor-1 α combined with Integra scaffold promotes healing of full-thickness skin defects

Jianting Gao1, Jianbiao Lin1, Guojun Liu1, Cong Zhu1, Benwen Wu1, Zhenqi Ding1, Guofeng Huang1,†()   

  1. 1. Department of Orthopeadics, Affiliated Southeast Hospital of Xiamen University, 909th Hospital of PLA Joint Service Support Uuit, Zhangzhou 363000, China
  • Received:2019-07-25 Published:2019-10-01
  • Corresponding author: Guofeng Huang
  • About author:
    Corresponding author: Huang Guofeng, Email:
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高建廷, 林剑彪, 刘国浚, 朱聪, 吴本文, 丁真奇, 黄国锋. 基质细胞衍生因子-1α联合Integra支架修复全层皮肤缺损创面的实验研究[J]. 中华损伤与修复杂志(电子版), 2019, 14(05): 355-360.

Jianting Gao, Jianbiao Lin, Guojun Liu, Cong Zhu, Benwen Wu, Zhenqi Ding, Guofeng Huang. Stromal cell-derived factor-1 α combined with Integra scaffold promotes healing of full-thickness skin defects[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2019, 14(05): 355-360.

观察基质细胞衍生因子-1α(SDF-1α)联合Integra支架促进全层皮肤缺损创面愈合的作用，并探讨其作用机制。

方法

选取6～8周龄的雄性健康C57小鼠30只，在其脊柱两侧对称部位分别作直径1 cm的圆形全层皮肤缺损创面，采用真皮支架Integra作为创面覆盖物。将30只小鼠背部左右对称创面按随机数字表法分为2组：SDF-1α组和对照组，各30个创面。SDF-1α组经皮下往创面内注射SDF-α，对照组皮下注射磷酸盐缓冲溶液。术后第3、6、12、18和24天观察创面的愈合时间和愈合创面收缩情况，并留取创面及周围组织标本行苏木精-伊红染色和免疫组织化学染色观察浸润细胞、肉芽组织厚度及血管化情况。对数据进行t检验。

结果

(1) SDF-1α组创面完全愈合时间为(15.7±1.6)d，明显短于对照组的(19.6±1.8)d，差异有统计学意义(t＝3.967，P<0.05)；(2)SDF-1α组术后第3、6、12天愈合创面收缩率分别为(7.3±3.3)%、(14.7±8.4)%、(27.6±6.3)%，与对照组[(8.3±2.5)%、(17.5±6.4)%、(31.2±16.5)%]比较，差异均无统计学意义(t＝0.6427、0.262、0.208，P值均大于0.05)；SDF-1α组术后第18、24天愈合创面收缩率为(36.6±6.7)%、(58.2±7.1)%，小于对照组[(67.6±10.7)%、(81.1±8.3)%]，差异均有统计学意义(t＝2.463、2.094，P值均小于0.05)；(3)创面肉芽组织术后第3天SDF-1α组浸润细胞数目为(181.7±28.8)个/视野，与对照组[(190.8±33.4)个/视野]比较，差异无统计学意义(t＝ 4.08, P<0.05)；术后第6天SDF-1α组浸润细胞数目[(382.2±43.4)个/视野]，与对照组[((478.2±38.8)个/视野]比较，差异无统计学意义(t＝ 6.20，P<0.05)；(4)肉芽组织的厚度术后第6、12天SDF-1α组创面的肉芽组织厚度为(255.8±41.8)、(387.6±36.8)μm，均小于对照组(407.3±43.4)、(490.2±49.4)μm],差异均有统计学意义(t＝4.08、6.159，P值均小于0.05)；(5)SDF-1α组术后第24天愈合创面与正常皮肤更为相似，对照组瘢痕明显，表皮薄；(6)SDF-1α组术后第12天创面肉芽组织中CD3、CD31阳性细胞的密度稍高于对照组，肉芽组织的血管密度明显高于对照组。

结论

局部使用SDF-1α可以促进全层皮肤缺损创面肉芽组织血管化，改善创面修复的效果。

关键词: 支架, 肉芽组织, 伤口愈合, 基质细胞衍生因子-1α, 血管化
Objective

To observe stromal cell-derived factor-1alpha (SDF-1a) combined with Integra scaffold promoting wound healing of full-thickness skin defects, and to explore its mechanism.

Methods

Thirty healthy male C57 mice aged 6-8 weeks were selected to make round full-thickness skin defect wounds with diameter of 1 cm on both sides of their spine symmetrically. The dermal scaffold Integra was used as the wound cover. The symmetrical wounds of thirty mice on the back were randomly divided into two groups: SDF-1a group and control group, with 30 wounds in each group. SDF-α was injected subcutaneously into the wound in the SDF-1α group, while phosphate buffer solution was subcutaneously into the wound in the control group. On days 3, 6, 12, 18 and 24 after operation, the wound healing time and contraction were observed, and the wound and surrounding tissue samples were taken for hematoxylin-eosin staining and immunohistochemical staining to observe the infiltrating cells, granulation tissue thickness and vascularization. Data were processed with t test.

Results

(1) The complete healing time of wounds in SDF-1a group was (15.7±1.6) days, significantly shorter than that in control group[(19.6±1.8) days], and the difference was statistically significant (t=3.967, P<0.05). (2) The wound healing contraction rates in SDF-1a group were (7.3±3.3)%, (14.7±8.4)%, (27.6±6.3)% respectively on days 3, 6 and 12 after operation, while those in control group (8.3±2.5)%, (17.5±6.4)%, (31.2±16.5)%. There were no statistical significant difference between the two groups (t=0.6427, 0.262, 0.208; with P value above 0.05). The wound healing contraction rates in SDF-1a group on days 18 and 24 after operation [ (36.6±6.7)%, (58.2 ±7.1)% ] were lower than those in control group[ (67.6±10.7)%, (81.1±8.3)% ]. The difference was statistically significant (t=2. 463, 2.094; with P value below 0.05). (3) The number of infiltrating cells per high-power field on day 3 after operation in SDF-1a group were (181.7±28.8), compared with those in control group were (190.8±33.4), there were no statistical difference (t=4.08, P>0.05). The number of infiltrating cells per high-power field on day 6 after operation in SDF-1a group were (382.2±43.4), compared with those in control group (478.2±38.8). There were statistical difference (t= 6.20, P<0.05). (4) The thickness of granulation tissue in SDF-1a group was (255.82±41.8) μm, (387.6 2±36.8) μm on day 6 and 12 after operation, which were smaller than those in control group [ (407.3±43.4) μm, (490.2 ± 49.4) μm]. The differences were significant (t=4.08, 6.159; with P value below 0.05). (5) The wound healing condition in SDF-1α group was consistent with normal skin on day 24 after operation, while the scar was apparent and the epidermis was thin in control group. (6) The density of CD3 and CD31 positive cells in the granulation tissue in SDF-1α group was slightly higher than that in control group on day 12 after operation. The vascular density of the granulation tissue in SDF-1α group was significantly higher than that in control group.

Conclusion

Local use of SDF-1alpha can promote the vascularization of granulation tissue in full-thickness skin defect wounds and improve the effect of wound repair.

Key words: Stents, Granulation tissue, Wound healing, Stromal cell-derived factor-1α, Vascularization
图1 2组小鼠全层皮肤缺损创面术后不同时间愈合情况的大体观察
表1 2组小鼠全层皮肤缺损创面术后不同时间愈合创面收缩率比较(%, ±s)
组别 创面数 术后第3天 术后第6天 术后第12天 术后第18天 术后第24天
SDF-1α组 6 7.3±3.3 14.7±8.4 27.6±6.3 36.6±6.7 58.2±7.1
对照组 6 8.3±2.5 17.5±6.4 31.2±16.5 67.6±10.7 81.1±8.3
t值 ? 0.643 0.262 0.208 2.463 2.094
P值 ? 0.267 0.801 0.844 0.048 0.044
图2 SDF-1α组和对照组术后第3、6天创面细胞浸润情况(苏木精-伊红染色　×100，图标尺标50 μm)
图3 SDF-1α组和对照组小鼠全层皮肤缺损创面术后第3、6天细胞浸润数量比较。与对照组比较，aP>0.05，bP<0.05。SDF-1α为基质细胞衍生因子-1α
图4 SDF-1α组和对照组术后第6、12天创面肉芽组织观察(苏木精-伊红染色　×40,图标尺标100μm)
图5 SDF-1α组和对照组小鼠全层皮肤缺损创面术后第6、12天的肉芽组织厚度比较。SDF-1α组与对照组比较，aP<0.05，bP<0.05。SDF-1α为基质细胞衍生因子-1α
图6 创面愈合后形态(苏木精-伊红染色　×40,图标尺标100 μm)
图7 SDF-1α组和对照组术后第12天创面的CD3、CD31阳性细胞的分布(免疫组织化学染色，图标尺标50 μm)
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