紫朱软膏通过抑制炎症反应促进糖尿病足溃疡愈合的研究  

Zizhu ointment promoteshealing of diabetic foot ulcers by inhibiting inflammatory reaction

作　　者：韩强[1] 柳国斌[1] 严仕梦 黄仁燕 徐烽 胡啸明[1] 施陈燕 杨晓[1] 王丽翔[1] 闫少庆[1] HAN Qiang;LIU Guo-bin;YAN Shi-meng;HUANG Ren-yan;XU Feng;HU Xiao-ming;SHI Chen-yan;YANG Xiao;WANG Li-xiang;YAN Shao-qing(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China)

机构地区：[1]上海中医药大学附属曙光医院,上海中医药大学,上海201203

出　　处：《海南医学院学报》2020年第21期1617-1624,1629,共9页Journal of Hainan Medical University

基　　金：国家自然科学基金面上项目(81774310);上海中医健康服务协同创新中心项目(ZYJKFW201701002);国家自然科学基金青年项目(81804095、81804096)。

摘　　要：目的:本研究旨在从炎症反应的角度探讨中药紫朱软膏在糖尿病足溃疡大鼠模型愈合中的作用机制。方法:采用高脂饲料配合链脲佐菌素(STZ)建立糖尿病模型,恒温恒压烫伤仪建立糖尿病足溃疡实验模型,通过普通溃疡模型与糖尿病足溃疡模型对照研究糖尿病足溃疡炎症反应的特点,通过对实验模型的干预对照包括生理盐水、西药贝复济、不同浓度梯度的紫朱软膏干预14 d,采用酶联免疫吸附法(ELISA)检测血清一氧化氮(NO)、C-反应蛋白(CRP)和白细胞介素-6(IL-6),蛋白质印迹法(WB)检测核因子-κB P65(NF-κB P65)、c-Jun N-末端激酶(JNK)、磷酸化磷脂酰肌醇3-激酶(P-PI3K),免疫组化法(IHC)检测创面组织的血管内皮生长因子(VEGF)和血小板内皮细胞黏附分子-34(CD34),冷原子吸收法检测血汞(Hg)含量,研究紫朱软膏对糖尿病足溃疡炎症的调控作用及药物安全性。结果:糖尿病足溃疡大鼠较普通溃疡炎症因子表达升高,紫朱软膏能够降低糖尿病足溃疡大鼠炎症因子(NO、CRP和IL-6)表达。糖尿病足溃疡模型中NF-κB、JNK、PI3K通路的激活,紫朱软膏能明显抑制JNK和NF-κB P65、PI3K的磷酸化,降低创面炎症反应,同时增加创面VEGF、CD34的表达,促进创面血管新生,同时对紫朱软膏用药大鼠血液汞含量的检测说明药物具有较好的安全性。结论:紫朱软膏能够通过抑制炎症相关途径促进糖尿病足溃疡组织修复,改善创面愈合,显示出紫朱软膏是一种安全有效的治疗糖尿病足溃疡的药物。Objective To explore the mechanism of Chinese medicine Zizhu ointment in healing of rat model with diabetic foot ulcers from the perspective of inflammatory response.Methods High-fat feed and streptozotocin(STZ)were used to establish diabetes,and an experimental model of diabetic foot ulcer was established with the constant temperature and constant pressure scaldapparatus.The groups received physiological saline,Western medicine Beifuji,and Zizhu ointment with different concentrations for 14 d,respectively.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum nitric oxide(NO),C-reactive protein(CRP)and interleukin-6(IL-6),Western blotting to measure nuclear factor-κBp65(NF-κB P65),c-Jun N-terminal kinase(JNK),phosphorylated phosphatidylinositol 3-kinase(P-PI3K),immunohistochemistry analysis to determine vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule-34(CD34)of wound tissues,and cold atomic absorption method to detect blood mercury(Hg)content.The effect of Zizhu ointment on the inflammation of diabetic foot ulcers and the safety of drugs were also studied.ResultsThe expression of inflammatory factors in diabetic foot ulcer rats was higher than that in ordinary ulcers.Zizhu ointment could reduce the expression of inflammatory factors(NO,CRP and IL-6)in diabetic foot ulcer rats.NF-κB,JNK,and PI3K pathways were activated.Zizhu ointment also significantly inhibited the phosphorylation of JNK,NF-κB P65,and PI3K,reduced the inflammation of the wound,increased the expression of VEGF,CD34 and promoted the wound angiogenesis.Besides,the results of blood mercury content in rats treated with Zizhu ointment indicate that the drug has good safety.Conclusion Zizhu ointment can promote tissue repair of diabetic foot ulcer and improve wound healing by inhibiting inflammation-related pathways,showing that Zizhu ointment is a safe and effective drug for the treatment of diabetic foot ulcers.

关 键 词：紫朱软膏 糖尿病足溃疡 炎症 汞 NF-ΚB 

分 类 号：R285.5[医药卫生—中药学]