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

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。

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

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