复方硝酸甘油凝胶对大鼠皮肤溃疡创面的调节作用

Effect of Compound Nitroglycerin Gel on Skin Ulcer Wound in Rats

目的研究复方硝酸甘油凝胶剂对大鼠皮肤溃疡的保护作用及其机制。方法建立54只大鼠皮肤溃疡模型,随机分成3组,每组18只,即模型对照组、京万红组、复方硝酸甘油凝胶剂组,观察创面大体情况及愈合时间,计数造模后第7天、第14天创面的成纤维细胞数、新生毛细血管数。采用反转录-聚合酶链反应(RT-PCR)法测定造模后第7天、第14天创面的血管内皮生长因子(VEGF)、血管生成素-1(Ang-1)、低氧诱导因子(HIF-1α)mRNA表达。结果与模型对照组比较[(24.17±5.91)d],复方硝酸甘油凝胶剂能明显缩短皮肤愈合时间[(14.67±3.76)d,P<0.01]。与模型对照组比较,复方硝酸甘油凝胶组增加造模后第7天创面中成纤维细胞[(61.20±7.56)个]和新生毛细血管数量[(9.35±1.43)个,P<0.05];上调VEGF(1.692±0.196)、HIF-1α(1.527±0.174)、Ang1(1.548±0.203)mRNA表达(P<0.05或P<0.01);降低造模后第14天创面中成纤维细胞(28.00±5.96)个和新生毛细血管数量[(4.20±1.30)个,(P<0.01)];下调VEGF(1.156±0.123)、HIF-1α(1.021±0.105)、Ang1(1.034±0.134)mRNA表达(P<0.05)。结论复方硝酸甘油凝胶剂通过调节成纤维细胞、新生毛细血管数量和VEGF/Ang1/HIF-1α信号转导通路达到治疗皮肤溃疡的作用。

Objective To study the protective effect of compound nitroglycerin gel on rats with skin ulcer wound and its action mechanism. Methods Skin ulcer model of 54 rats was established.Then the rats were randomly divided into three groups（ n = 18 each）,including model control group,Jin wan hong group,and compound nitroglycerin gel group. Wound healing process and healing time were recorded.At the day 7 and 14 after the model was established,the number of fibroblasts and new blood capillaries of granulation tissue from center of the wound were measured,and RT-PCR was used to detect mRNA expression levels of VEGF,Ang1 and HIF-1α. Results As compared with model control group [（ 24. 17 ± 5. 91） days],healing time of skin in the compound nitroglycerin gel group was significantly shorter [（ 14.67±3.76） days,P〈0.01].The numbers of fibroblasts（ 61.20±7.56） and new blood capillaries（ 9.35±1.43） were increased,and mRNA expression levels of VEGF（ 1.692±0.196）,HIF-1α（ 1.527±0.174） and Ang1（ 1.548±0.203） were remarkably up-regulated on 7thday（ P〈0.05 or P〈0.01）.While on 14 th day,the numbers of fibroblasts（ 28.00±5.96） and new blood capillaries（ 4.20±1.30） were decreased and the mRNA expression levels of VEGF（ 1.156±0.123）,HIF-1α（ 1.021±0.105） and Ang1（ 1.034±0.134） were significantly down-regulated（ P〈0.05 or P〈0.01）. Conclusion Compound nitroglycerin gel can treat skin ulcer wound via regulating the numbers of fibroblasts,new blood capillaries and VEGF / Ang1 / HIF-1α signal transduction pathway.