利用基因芯片技术阐述中药解毒生肌膏对大鼠糖尿病足溃疡作用的分子机制
A microarray study on the molecular mechanism for the therapeutic effect of Antidotal and Myogenic Ointmen(解毒生肌膏)on the foot ulcer in diabetic rats
摘要目的 采用基因芯片技术探讨中药解毒生肌膏对大鼠糖尿病足溃疡的作用机制.方法 腹腔注射链脲佐菌素复制糖尿病大鼠模型,喂养到6个月时结扎腘动脉下端并切断,7个月时造成足底部皮肤深Ⅱ度烫伤复制大鼠糖尿病足溃疡模型.将模型大鼠按随机数字表法分为中药组、表皮生长因子组、模型对照组,每组15只.烫伤后分别给予中药解毒生肌膏、重组人表皮生长因子、生理盐水局部外用,每2d换药1次,治疗30 d后观察大鼠治疗前后溃疡面积及愈合情况.提取各组溃疡区组织总RNA,应用大鼠细胞因子芯片进行组间基因比较.结果 与模型对照组比较,表皮生长因子组有25个基因发生改变,其中上调23个,下调2个;中药组有30个基因发生改变,其中上调29个,下调1个.与表皮生长因子组比较,中药组有16个基因发生改变,其中上调11个,下调5个.这些基因涉及神经营养因子、趋化因子.结论 中药解毒生肌膏和表皮生长因子能够通过影响各种炎症反应过程中的细胞因子平衡,促进糖尿病足溃疡的愈合,其中以中药解毒生肌膏的效果更好.
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abstractsObjective To investigate the underlying mechanism for the therapeutic effect of a traditional Chinese medicinal recipe,Antidotal and Myogenic Ointment(解毒生肌膏,AMO),on the foot ulcer in diabetic rat using cDNA microarray technology.Methods 45 rats were made diabetic by i.p.injection of streptozocin.The treated animals were then fed for 6 months,and subjected to the dissection of distal popliteal artery after ligation of the vessels.Another month later,grade Ⅱ burn injury was produced on the bottom of their foot as a model of diabetic foot ulcer.The rats were then randomly divided into three groups (15 each) to receive AMO,epidermal growth factor (EGF) and saline for 30 days,with dressing change in every 2 days.The area of ulcer wound and their healing rate were recorded before and after the treatment.Total RNA was extracted from the tissue samples collected near the wound,and the expression profile of cytokine genes demonstrated using the microarry for rats.Results In comparison with the saline group difference in the level of expression was found in 25 genes (23 0f them were up-regulated and 2 down-regulated) in EGF group,and 30 genes in AMO groups (29 0f them up-regulated and l down-regulated).In comparison with EGF group,difference in level of expression was found in 16 genes in AMO group,with 11 up-regulated and 5 down-regulated.Neurotrophic factors and chemotactic factors,etc were among the genes involved.Conclusion In comparison with EGF,AMO is more effective in the treatment of foot ulcer in diabetic rats.It is possible that AMO produces such effects through the regulation of balance in cytokine expression.
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