血余蛋黄油对表柔比星致慢性皮肤溃疡疮面愈合及氧化应激反应调节作用的实验研究

Regulative effect of Xueyudanhuang Ointment on cicatrization and oxidative stress during chronic dermal ulceration induced by epirubicin

目的探讨血余蛋黄油对表柔比星致小鼠表皮溃疡及疮面氧化应激反应的影响。方法Balb/c雄性小鼠72只,表柔比星2 g/L皮内注射制备慢性皮肤溃疡动物模型,随机分为4组:模型组、重组人表皮细胞生长因子组(生长因子组)、维生素E衍生物Trolox组(Trolox组)、血余蛋黄油组,每组18只,隔日换药1次直至溃疡愈合,造模后第13天、第27天每组各取材6只,另设正常对照组10只。采用Image Pro-plus图像软件分析疮面面积,分光光度计法检测疮面组织超氧化物歧化酶(SOD)、脂质过氧化物(MDA)水平,HE、Masson、天狼星红染色观察疮面组织形态学及胶原变化。结果血余蛋黄油能够促进疮面结痂,缩短溃疡愈合时间,平均愈合时间由对照组的29.75 d缩短至26.16 d,与生长因子组26.29 d接近;并能够促进溃疡疮面的表皮细胞及胶原修复;造模后13 d疮面组织氧化应激损伤明显,SOD活力为(9.67±2.80)U/mg,MDA为(15.48±3.72)μmol/g,血余蛋黄油治疗后SOD活力提高为(16.64±5.20)U/mg,MDA水平降低为(10.86±1.30)μmol/g,与对照组比较差异显著,P<0.05。造模后27 d疮面组织基本愈合,各组SOD活力及MDA水平接近正常水平。结论血余蛋黄油能够促进皮肤溃疡小鼠疮面结痂,缩短愈合时间;其作用机制与其能够促进疮面表皮细胞及胶原修复,降低疮面组织脂质过氧化损伤,提高抗氧化能力有关。

Objective To investigate the influence of Xueyudanhuang Ointment on dermal ulceration and oxidative stress induced by epirubicin in mice. Methods The model of chronic dermal ulceration was established by the intradermal injection of epirubicin （2 g/L） in 72 Balb/c male mice, and then the mice were randomly divided into 4 groups （each n = 18 ）, including the model group, recombinant human epidermal growth factor （rh-EGF） group, Trolox group and Xueyudanhuang Ointment group. The drugs were administrated every other day until the dermal ulceration healing. After 13 and 27 days 6 mice were chosen from each group respectively and the control group was set up （n = 10）. The ulceration area was analyzed by using Image Pro-plus software, the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were detected by using spectrophotometer, and the histological and collagen changes in ulceration were observed by using the stain methods of HE, Masson and Sirius red. Results Xueyudanhuang Ointment improved the healing of dermal ulceration. The average healing time was shortened from 29.75 days in the control group to 26.16 days in the Xueyudanhuang Ointment group, which was almost as the same as that in the rhEGF group （26.29 days）. Xueyudanhuang Ointment also promoted the repairing of epidermal cells and collagen of dermal ulceration. The injury of oxidative stress was serious 13 days after the model establishment, showed as SOD activity was （9.67 ±2.80） U/mg, and MDA level was （15.48 ± 3.72） μmol/g. After the treatment with Xueyudanhuang Ointment SOD activity increased to （16.64 ± 5.20） U/rag and MDA level decreased to （10.86± 1.30） μmol/g. There was a significant difference compared with those in the control group （P 〈 0.05）. The wlceration was healed initially 27 days after the establishment of the model , and SOD activities and MDA levels were almost normal in all group. Conclusion Xueyudanhuang Ointment can improve the scabbing of dermal ulceration, shorten the healing time. The mechanism may be related to that it can promote the repairing of epidermal cells and collagen of dermal ulceration, relieve the injury of oxidative stress and increase the antioxidant activity in mice.