苯妥英钠对大鼠创面愈合的影响

Experimental study on influence of phenytoin sodium on wound healing in rats

目的观察苯妥英钠对实验大鼠创面愈合过程的影响,探讨其作用机制。方法 100只SD大鼠随机分为5组,分别为空白对照组、紫草油阳性对照组和苯妥英钠小剂量组(5 mg/cm^2)、中剂量组(10 mg/cm^2)、高剂量组(20 mg/cm^2),每组20只。大鼠背侧脊柱旁设计2 cm×3 cm矩形创面模型。于创伤后4、8、12、16 d观察创面愈合率并采用免疫组化方法检测创面Ⅰ型胶原蛋白、血管内皮生长因子(VEGF)、Bcl-2、Bax的表达。结果苯妥英钠小剂量组在创伤后8、12、16 d创面愈合率均明显优于空白对照组及苯妥英钠中、高剂量组(P<0.05)。Ⅰ型胶原蛋白、VEGF、Bcl-2、Bax阳性表达呈逐渐增加趋势。Bax的表达以苯妥英钠中、高剂量组增加最为明显,高剂量组在创伤后16 d与小剂量组、空白对照组、紫草油组差异有统计学意义(P<0.05)。Ⅰ型胶原蛋白在苯妥英钠高剂量组表达增加最少,创伤后16 d高剂量组与小剂量组、空白对照组、紫草油组差异有统计学意义(P<0.05)。创伤后4 d,VEGF在苯妥英钠小剂量组的表达明显增加,16 d时,VEGF在紫草油阳性对照组与苯妥英钠小剂量组的表达已无统计学意义,但与其他组比较差异有统计学意义(P<0.05)。创伤后4d,Bcl-2在苯妥英钠小剂量组与紫草油组的表达同步增加,16d时仍高于其他各组(P<0.05),苯妥英钠高、中剂量组表达低于空白对照组(P<0.05)。结论苯妥英钠小剂量组能够通过促进成纤维细胞增殖、血管再生、细胞外基质沉积等方面促进创面愈合。

Objective To investigate the effect and mechanism of phenytoin sodium on rats skin wound heal- ing. Methods 100 SD rats were divided randomly into normal control group, positive control group （puccoon oil）, the phenytoin sodium group （5, 10, 20 mg/cm2）, 20 rats each group. A rectangular wound （diam = 2 cmx 3 cm） was made on the back of rats（phenytoin sodium）, then observed the wound healing rate, the expression of collagen type I, vascular endothelial growth factor （VEGF）, Bcl-2 and Bax on the days 4th, 8th, 12th, 16th after injury. Results Compared with normal control group and the group treated with phenytoin sodium （10, 20 mg/cm2）, the wound healing rate of group（5 mg/cm2） remarkably higher at the 8th, 12th, and 16th days after injury（ P 〈 0.05）. Immunochemistry showed that the positive rates of collagen type I, VEGF, Bcl- 2 and Bax tended to gradually increase with time passing. The expression of Bax increased obviously in the group treated with phenytoin sodium（ 10, 20 mg/cm2）, and the high dose group（20 mg/cm2） was significantly different with the other groups at the 16th day except for the middle dose group （ P 〈 0.05 ）; the expression of type I collagen with phenytoin sodium（20 mg/cm~） shows the least increast, there are significant differences at the 16th day between phenytoin sodium（20 mg/cm2） and 5 mg/cm2 group, control group, and puccoon oil group （ P 〈 0.05）. The expression of VEGF increased significantly in the phenytoin sodium （5 mg/cm2） from the 4 days after injury, its expression between positive control group and phenytoin sodium （5 mg/cm2） at 16th days, was found no significant differences, but it clearly distinguishable from the other groups（ P 〈 0.05 ）. The expression of Bcl-2 increased simultaneously in phenytoin sodium group （5 mg/cm2） and positive control group from the 4 days after injury, there were still a significant difference compared with the other groups on 16 th after injury（ P 〈 0.05）, and the expression of Bcl-2 in normal control group was higher than the groups treated with phenytoin sodium 10, 20 mg/cm2（ P 〈 0.05 ）. Conclusion The group treated with phenytoin sodi- um （5 mg/cm2） can accelerate wound healing obviously, potentially through the proliferation of fibroblast, re- vascularization and deposition of extracellular matrix.