文献类型：期刊文献

中文题名：基于AGEs-RAGE/NF-κB信号通路探讨生肌玉红膏促进糖尿病足溃疡模型大鼠创面组织愈合的作用机制

英文题名：Mechanism of Shengji Yuhong Ointment(生肌玉红膏)in promoting wound healing in diabetic foot ulcer model rats based on AGE-RAGE/NF-κB signaling pathway

作者：张建平[1];王玮[1];石育弘[1];董小鹏[1];赵春霖[1];王丽娟[2];曾昭洋[3]

第一作者：张建平

机构：[1]甘肃中医药大学附属医院外科,甘肃兰州730020;[2]甘肃中医药大学药学院,甘肃兰州730101;[3]甘肃中医药大学中西医结合学院,甘肃兰州730101

第一机构：甘肃中医药大学第二附属医院

年份：2024

卷号：41

期号：5

起止页码：1

中文期刊名：甘肃中医药大学学报

外文期刊名：Journal of Gansu University of Chinese Medicine

基金：甘肃省高等学校创新基金项目(2021B-170);甘肃省自然科学基金项目(21JR11RA160);甘肃省自然科学基金委员会一般项目(20JR5RA179)。

语种：中文

中文关键词：生肌玉红膏;糖尿病足溃疡;创面修复;晚期糖基化终产物(AGEs)/晚期糖基化终产物受体(RAGE)/核转录因子-κB(NF-κB)信号通路;作用机制

外文关键词：Shengji Yuhong Ointment(生肌玉红膏);diabetic foot ulcer;wound healing;advanced glycation end products(AGEs)/advanced glycation end products receptor(RAGE)/nuclear transcription factor-kB(NF-kB)signaling pathway;action mechanism

摘要：目的基于晚期糖基化终产物(AGEs)-晚期糖基化终产物受体(RAGE)/核转录因子-κB(NF-κB)信号通路探讨生肌玉红膏促进糖尿病足溃疡模型大鼠创面组织愈合的潜在作用机制。方法将60只SPF级雄性大鼠采用随机数字表法分为空白组、模型组、爱可欣组、生肌玉红膏组4组,每组15只。除空白组外,其余各组采用20%蔗糖水及高脂饲料喂养、链脲佐菌素腹腔注射联合足底损伤法建立大鼠糖尿病足溃疡模型,并分别给予相应处理。比较致创后第3,7,15天各组大鼠体质量、随机血糖、湿热毒盛证候评分、创面愈合率,以及创面皮肤组织肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、C反应蛋白(CRP)、AGEs、RAGE含量;观察并比较致创后第3,7,15天各组大鼠创面皮肤组织病理学改变;采用Western blot法检测各组致创后第3,15天核转录因子-κB(NF-κB)p65蛋白表达水平。结果与空白组比较,致创后第3,7,15天模型组体质量明显下降,随机血糖,湿热毒盛证候评分,创面皮肤组织TNF-α、IL-6、CRP、AGEs、RAGE含量,致创后第7,15天创面愈合率均明显升高(P<0.05或P<0.01);与模型组比较,致创后第7,15天爱可欣组及生肌玉红膏组湿热毒盛证候评分,创面愈合率,创面皮肤组织TNF-α、IL-6、CRP含量均明显降低,致创后第7,15天生肌玉红膏组创面皮肤组织AGEs含量均明显降低,致创后第3,7,15天生肌玉红膏组创面皮肤组织RAGE含量均明显降低(P<0.05或P<0.01);爱可欣组及生肌玉红膏组可不同程度地改善模型组大鼠创面皮肤结构紊乱,炎症细胞浸润,肌腱胶原纤维排列疏松、断裂等情况;与空白组比较,致创后第3,15天模型组创面皮肤组织NF-κB p65蛋白表达水平均明显升高(P<0.01);与模型组比较,致创后第3,15天生肌玉红膏组创面皮肤组织NF-κB p65蛋白表达水平均明显降低(P<0.05)。结论生肌玉红膏可通过抑制AGEs/RAGE/NF-κB信号通路促进糖尿病足溃疡模型大鼠创面修复愈合。
Objective To explore the potential mechanism by which Shengji Yuhong Ointment(生肌玉红膏)facilitates wound healing in diabetic foot ulcer model rats based on the advanced glycation end-product receptor(RAGE)/nuclear transcription factor-κB(NF-κB)signaling pathway.Methods 60 SPF-grade male rats were randomly divided into four groups using a random number table:the blank group,the model group,the Acasin group,and the Shengji Yuhong Ointment group,with fifteen rats in each group.With the exception of the blank group,the remaining groups were fed with 20%sucrose water and a high-fat diet,and intraperitoneal injection of streptozotocin combined with plantar injury was employed to establish the rat model of diabetic foot ulcer,and each group was administered the corresponding treatment respectively.The body weight,random blood glucose,syndrome score of dampness-heat toxicity,wound healing rate,and the contents of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),C-reactive protein(CRP),advanced glycation end products(AGEs),and RAGE of wound skin tissue in all groups were compared at 3,7,and 15 days after the injury.The histopathological changes of wound skin were observed and compared on the 3rd,7th,and 15th day after injury.Western blot was utilized to detect the expression of nuclear factor-κB(NF-κB)p65 on the 3rd and 15th day after injury in each group.Results Compared with the blank group,the body weight of the model group decreased significantly on the 3rd,7th,and 15th day after injury,while the random blood glucose,the syndrome score of dampness-heat toxicity,the content of TNF-α,IL-6,CRP,AGEs,and RAGE in the wound skin tissue increased significantly,and the wound healing rate increased significantly on the 7th and 15th day after injury(P<0.05 or P<0.01).Compared with the model group,the syndrome score of dampness-heat toxicity,the wound healing rate,and the contents of TNF-α,IL-6 and CRP in the wound skin tissue of the Acasin group and the Shengji Yuhong Ointment group decreased significantly on the 7th and 15th day after injury.The content of AGEs in the wound skin tissue of Shengji Yuhong Ointment group decreased significantly on the 7th and 15th day after injury.The content of RAGE in the wound skin tissue of the Shengji Yuhong Ointment group decreased significantly on the 3rd,7th,and 15th day after injury(P<0.05).The Acasin group and the Shengji Yuhong Ointment group could ameliorate the disordered skin wound structure,the large number of inflammatory cell infiltrations,and the loose and broken tendon collagen fiber arrangement in the model group.Compared with the blank group,the expression level of NF-κB p65 in the wound skin tissue of the model group increased significantly on the 3rd and 15th day after induction(P<0.01).Compared with the model group,the expression level of NF-κB p65 in the wound skin tissue of the Shengji Yuhong ointment group decreased significantly on the 3rd and 15th day after injection(P<0.05).Conclusion Shengji Yuhong Ointment can promote wound healing in the diabetic foot ulcer model rats by inhibiting the AGEs/RAGE/NF-κB signaling pathway.