皮肤全层缺损牵张闭合后罂粟碱对创面愈合的影响

Effect of papaverine on wound healing of full-thickness skin defect after skin stretching

目的探讨猪皮肤全层缺损牵张闭合后罂粟碱对创面愈合的影响。方法8只巴马香猪,每头猪两侧前肢中段分别制作7 cm×7 cm标准皮肤全层缺损创面,均采用皮肤牵张术关闭创面。采用随机数字表法将8只巴马香猪分为实验组(4只)和对照组(4只),比较两组动物术前及术后即刻创缘经皮氧分压(TcPO2)和术后4 d、10 d伤口临床愈合评分,Weidner方法计数法检测术后当天、10 d创缘组织微血管密度(MVD),运用免疫组化法检测术后当天、4 d、10 d创缘组织缺氧诱导因子-1ɑ(HIF-1ɑ)与血管内皮生长因子(VEGF)的表达。结果术前实验组和对照组TcPO2分别为(55.1±5.4)mmHg和(54.7±5.9)mmHg(P>0.05),术后实验组TcPO2为(22.7±3.3)mmHg,高于对照组的(16.4±3.4)mmHg(P<0.01)。术后4 d实验组和对照组伤口临床愈合评分分别为(2.1 ± 0.4)分和(2.6 ± 0.7)分(P>0.05);术后10 d实验组临床愈合评分为(1.3±0.5)分,优于对照组的(4.6 ± 0.7)分(P<0.01)。术后当天实验组与对照组MVD值分别为(9.3±1.2)个与(8.5±1.3)个(P>0.05),而术后10 d实验组MVD为(29.5±4.8)个,显著高于对照组的(21.1±3.4)个(P<0.01)。术后4 d实验组HIF-1α表达(50.0±7.0)显著高于对照组(38.6±7.0)(P<0.01),而术后当天与10 d两组间HIF-1ɑ的表达差异均无统计学意义(P>0.05)。术后4 d实验组VEGF的表达(49.9±10.8)高于对照组(39.2±6.3)(P<0.05),而术后当天与10 d两组VEGF表达差异均无统计学意义(P>0.05)。结论猪皮肤全层缺损牵张闭合后,应用罂粟碱可缓解小血管痉挛,改善创面氧供,促进创面的微血管生长,从而促进创面愈合,可能与HIF-1ɑ及VEGF等调控因子表达升高有关。

Objective To investigate the effect of papaverine on wound healing of full-thickness skin defect after skin stretching in swine. Methods Eight Bama pigs were prepared. Standard full-thickness skin defect for 7 cm×7 cm was produced in the middle part of each pig's forelimb, and skin traction was used to close the wound. According to random number table method, the pigs were divided into experiment group and control group, with four pigs in each group. Percutaneous oxygen partial pressure (TcPO2) was compared preoperatively and postoperatively. Wound healing clinical score was evaluated four and 10 days after operation. Weidner counting method was employed to determine the microvascular density (MVD) of the wound edge tissue 0 and 10 days after operation. Immunohistochemistry was used to observe the expression of hypoxia inducible factor 1-α(HIF- 1α) and vascular endothelial growth factor (VEGF) 0, 4 and 10 days after operation. Results There was no statistically significant difference in TcPO2 between the experiment group [(55.1±5.4)mmHg] and the control group [(54.7±5.9)mmHg] before skin stretching (P>0.05), while statistically significant difference was found after stretching [(22.7±3.3)mmHg vs.(16.4±3.4)mmHg](P<0.01). There was no statistically significant difference in clinical wound healing scores between the control group and experiment group 4 days after skin stretching [(2.6±0.7)points vs.(2.1±0.4)points](P>0.05), but better result was found in experiment group compared with the control group in 10 days [(1.3±0.5)points vs.(4.6±0.7)points](P<0.01). MVD of skin tissue showed no statistically significant difference between the control group (8.5±1.3) and the experiment group (9.3±1.2) immediately after skin stretching (P>0.05), while the MVD of wound skin tissue in the experiment group (29.5±4.8) was significantly higher than that in the control group (21.1±3.4) 10 days after skin stretching (P<0.01). After skin stretching, the HIF-1 alpha expression in experiment group was significantly higher than the control group 4 days after skin stretching [(50.0±7.0) vs.(38.6±7.0)](P<0.01), but no statistical significance was found between that at 0 day and 10 days(P>0.05). The expression of VEGF in the wound skin tissues of the experiment group was significantly higher than that of the control group [(49.9±10.8) vs.(39.2±6.3)] at 4 days after skin stretching (P<0.05), while no statistically significance was found at 0 and 10 days (P>0.05). Conclusion For full-thickness skin defect after skin stretching in pigs, papaverine can alleviate small vessel spasm, improve skin edge oxygen supply, and promote the growth of microvessels, thus promoting the healing, which might be associated with the increase of HIF-1ɑ and VEGF expression.