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改良生肌玉红膏通过AGEs/RAGE/PI3K/AKT通路调控巨噬细胞极化促进糖尿病足溃疡愈合的机制
石波,张轩,李然,刘剑刚,庄百溪,徐浩
中国中医科学院西苑医院北京 100091
摘要:
目的:探讨改良生肌玉红膏通过AGEs/RAGE/PI3K/AKT通路调控巨噬细胞极化,促进糖尿病足溃疡(DFU)愈合的机制。方法:将40只SD雄性大鼠随机分为空白组(n=8)和糖尿病大鼠(n=32),糖尿病大鼠采用链脲佐菌素(STZ)诱导制备糖尿病模型并致创形成DFU模型,成模后随机分为模型组、西药组(含银藻酸盐敷料组)、原方生肌玉红膏组、改良生肌玉红膏组,每组8只。采用HE染色观察大鼠创面组织形态,CD86、CD206免疫组化检测创面M1/M2巨噬细胞变化情况;ELISA法检测创面组织中白细胞介素(IL)-1β、IL-6、IL-4、IL-10、精氨酸酶-1(Arg-1)、基质金属蛋白酶-9(MMP-9)浓度,Western blot检测大鼠溃疡创面组织晚期糖基化终末产物(AGEs)、晚期糖基化终末产物受体(RAGE)、磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B(AKT)蛋白表达水平。结果:改良生肌玉红膏组巨噬细胞由M1向M2极化较模型组更明显(P <0.05)。与模型组及原方生肌玉红膏组相比,改良生肌玉红膏组DFU大鼠创面组织IL-1β、IL-6、MMP-9蛋白表达均降低(P <0.05),IL-4、IL-10、Arg-1的表达均升高(P <0.05)。空白组与改良生肌玉红膏组AGEs表达差异无统计学意义(P >0.05),模型组及西药组的AGEs表达高于空白组(P <0.05)。与模型组相比,改良生肌玉红膏组AGEs、RAGE和AKT明显下降(P <0.05),与西药组相比,改良生肌玉红膏组AGEs、PI3K和AKT明显下降(P <0.05)。与原方生肌玉红膏组相比,改良生肌玉红膏组AKT明显下降(P <0.05)。结论:改良生肌玉红膏可促进DFU愈合,其机制可能与通过AGEs/RAGE/PI3K/AKT信号通路调控巨噬细胞极化,改善DFU炎症状态有关。
关键词:  糖尿病足溃疡  生肌玉红膏  PI3K/AKT信号通路  AGEs/RAGE信号通路  巨噬细胞极化
DOI:10.3969/j.issn.1007-6948.2026.02.018
投稿时间:2025-07-07
基金项目:中国中医科学院科技创新工程重大攻关项目(CI2021A01909)
Mechanism of modified Shengji Yuhong ointment regulating M1/M2 polarization of macrophages via AGEs/RAGE/PI3K/AKT pathway to promote healing of diabetic foot ulcer
SHI Bo,ZHANG Xuan,LI Ran
Xiyuan Hospital of Chinese Academy of Traditional Chinese Medicine,Beijing100091,China
Abstract:
Objective To explore the mechanism of modified Shengji Yuhong ointment in promoting the healing of diabetes foot ulcer (DFU) based on animal experiments. Methods Forty male SD rats were randomly divided into blank group (n=8) and diabetes group (n=32). Record the changes in wound size of each group of rats during the experiment. HE staining was used to observe the morphology of rat wound tissue, and CD86 and CD206 immunohistochemistry were used to detect changes in M1/M2 macrophages in the wound; ELISA was used to detect the concentrations of IL-1β, IL-6, IL-4, IL-10, Arg-1, and MMP-9 in wound tissues, and Western blot was used to detect the expression of AGEs-RAGE-PI3K-AKT protein in rat ulcer wound tissues. Results Modified Shengji Yuhong ointment can reduce the concentrations of IL-1β, IL-6, and MMP-9 in ulcer tissue of DFU rats, increase the concentrations of IL-4, IL-10, and Arg-1, significantly reduce the inflammation of ulcer wounds in DFU rats, regulate the polarization of M1/M2 macrophages and the expression of AGEs, RAGE, PI3K, and AKT proteins in ulcer wounds. Conclusion The modified Shengji Yuhong ointment can promote the healing of DFU, and its mechanism may be related to regulating macrophage polarization and improving the inflammatory state of DFU through the AGEs/RAGE/PI3K/AKT signaling pathway.
Key words:  Diabetic foot ulcer  Shengji Yuhong ointment  PI3K/AKT signaling pathway  AGEs/RAGE signaling pathway  macrophage polarization

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