卡托普利对兔耳增生性瘢痕影响的实验研究

Effect of captopril on scar hyperplasia in rabbit ears

目的研究在创伤后不同时期使用卡托普利对兔耳增生性瘢痕的影响。方法16只新西兰兔按照随机数字表法分为4组（每组4只），每只兔耳腹侧制作6个直径1cm的圆形创面。早期治疗组在创面形成后立即给予卡托普利口服治疗；晚期治疗组在术后第21天开始予卡托普利口服治疗；阳性对照组在术后第21、28天分别给予皮损内曲安奈德溶液注射治疗；阴性对照组不给予任何干预。观察并记录创面完全上皮化时间。在术后第42天，根据温哥华瘢痕量表（VSS）对瘢痕进行评分。计算瘢痕增生指数（SEI）。所有标本行苏木精-伊红染色和苦味酸天狼星红染色后，观察成纤维细胞数量、I型胶原面密度和Ⅲ型胶原面密度。结果①创面完全上皮化时间：多组间比较差异无统计学意义（F=0．75，P=0．97）。②vss分值和SEI多组间比较差异均有统计学意义（F=83．44，P〈0．05；F=106．91，P〈0．05）；阳性对照组[（3．1±1．5）分，1．33±0．13]〈早期治疗组[（4．0±1．2）分，1．56±0．15]〈晚期治疗组[（6．0±1．4）分，1．73±0．16）]〈阴性对照组[（6．8±1．0）分，2．02±0．29]。③成纤维细胞数量多组间比较差异有统计学意义（F=211．76，P〈0．05）；阳性对照组（233±62）个〈早期治疗组（380±53）个、晚期治疗组（389±64）个〈阴性对照组（612±107）个。④I型胶原面密度多组间比较差异有统计学意义（F=480．53，P〈0．05）；早期治疗组（36．1±1．6）％、阳性对照组（36．4±2．4）％〈晚期治疗组（47．7±2．0）％〈阴性对照组（49．5±2．8）％。⑤HI型胶原面密度多组间比较差异有统计学意义（F=39．23，P〈0．05）；早期治疗组（26．0±1．8）％〈晚期治疗组（28．2±1．4）％、阳性对照组（27．9±2．3）％〈阴性对照组（29．8±1．4）％。结论卡托普利可通过抑制成纤维细胞增殖及细胞间基质沉积而抑制兔耳瘢痕增生，创伤后立刻使用治疗效果可能更佳。

Objective To investigate the effect of captopril on hyperplastic scar formation in different stages of traumatic wound in rabbit ears. Methods Sixteen healthy New Zealand rabbits were randomly divided into 4 groups （n =4 in each group） ; the rabbits had 6 1-cm-diameter circular full-thickness skin wounds on each ear. The early treatment group took captopril immediately after trauma. The late treatment group was treated with captopril on the 21th day after operation. The positive control group was injected triamcinolone acetonide in the wound on the 21th and 28 days after operation. The bland control group had no special treatment. The time of wound healing（ complete epithelization） was recorded. The Vancouver Scar Scale（VSS） was evaluated on the 42th day after operation. The scar elevation index（ SEI）, the number of fibroblasts and areal densities of type Ⅰ ,Ⅲ collagen were analyzed. Results （1）Wound healing time had no significant differences among groups （F = 0. 75, P =0. 97）. （2）VSS score and SEI had significant differences among groups（F = 83.44, P 〈 0. 05 ; F = 106. 91, P 〈 0. 05） ： positive control group [ （3. 1 ± 1.5 ） score, 1.33 ±0. 13 ] 〈 early treatment group [ （4. 0 ±1. 2 ） score, 1.56±0.15] 〈 late treatment group[（6.0 ± 1.4） score, 1.73±0.16] 〈 blank control group[（6.8 ± 1.0） score, 2.02±0. 29]. （3）The number of fibroblasts had significant differences among groups（ F = 211.76, P 〈 0. 05） ： positive control group （ 233 ± 62 ） 〈 early treatment group （ 380 ± 53 ）, late treatment group （ 389 ±64） 〈 blank control group（612 ± 107）. （4）Areal density of type I collagen had significant differences among groups （ F = 480. 53, P 〈 0. 05） ： early treatment group （36. 1 ± 1.6） % （5） positive control group （ 36. 4 ±2. 4） % 〈late treatment group （47.7 ±2. 0）% 〈 blank control group （49.5 ± 2. 8 ）%. （6）Areal density of type Ⅲ collagen had significant differences among groups （ F = 39. 23, P 〈 0. 05 ） ： early treatment group （ 26. 0 ± 1.8 ） % 〈 late treatment group （28.2± 1.4）% ≈ positive control group （27.9 ± 2. 3 ）% 〈 blank control group （29. 8 ± 1.4）%. Conclusions Captopril inhibits proliferation of fibroblasts and deposition of extracellular matrix, and it prevents scar hyperplasia in rabbit ears. Administration of captopril immediately after trauma is optimistic.