现代中西医结合杂志2025,Vol.34Issue(8):1043-1049,7.DOI:10.3969/j.issn.1008-8849.2025.08.004
基于BNIP3/NIX信号通路介导的线粒体自噬探讨复方蛋黄油膏对糖尿病溃疡小鼠创面愈合的影响
Effect of compound egg yolk ointment on wound healing in mice with diabetic ulcers based on mitochondrial autophagy mediated by BNIP3/NIX signaling pathway
摘要
Abstract
Objective It is to observe the effect of compound egg yolk ointment on wound healing in mice with diabetic ulcers,and to explore its mechanism based on mitochondrial autophagy mediated by Bcl-2/adenovirus E1B 19kDa interac-ting protein 3(BNIP3)/NIP3-like protein X(NIX)signaling pathway.Methods Twenty male SPF db/db mice were ran-domly divided into control group,model group,compound egg yolk cream group,BNIP3 overexpression group and com-pound egg yolk ointment+BNIP3 silence group,with 4 mice in each group.The mice of all groups except for the control group were prepared to establish models of whole skin defect ulcers.After modeling,the compound egg yolk ointment group and compound egg yolk ointment+BNIP3 silence group were treated with compound egg yolk ointment daily by external ap-plication,while the compound egg yolk ointment+BNIP3 silence group was injected with BNIP3-siRNA via the tail vein ev-ery other day;the BNIP3 overexpression group and the model group were given saline dressing changes for wounds,while the BNIP3 overexpression group was injected with BNIP3 overexpression plasmid via the tail vein every other day;the con-trol group was given saline wipe on back skin.Each group was intervened continuously for 21 days.The wound healing of mice in each group was observed on the 7th,14th and 21st days after modeling;the wound tissue of mice was taken on the 21st day of modeling,and the histopathological morphology of the wound lesions,angiogenesis and number of fibroblasts were observed by HE staining and immunohistochemical staining,the expression of BNIP3 and NIX proteins in the wound tissues were detected by Western blot method.Results The wound healing rates of mice in the compound egg yolk ointment group and BNIP3 overexpression group were significantly higher than those of the model group and compound egg yolk oint-ment+BNIP3 silence group at all time points(all P<0.05),and there was no statistically significant difference between the compound egg yolk ointment group and BNIP3 overexpression group,or between the model group and compound egg yolk ointment+BNIP3 silence group(both P>0.05).HE staining and immunohistochemical staining showed that there were fewer inflammatory cells,more blood vessels and fibroblasts,and collagen fibers tended to be arranged orderly in the compound egg yolk ointment group and BNIP3 overexpression group than those in the model group and compound egg yolk ointment+BNIP3 silence group.The relative expressions of BNIP3 and NIX proteins in traumatic tissues of the compound egg yolk ointment group and BNIP3 overexpression group were significantly higher than those in the model group and com-pound egg yolk ointment+BNIP3 silence group(all P<0.05),and there was no statistically significant difference between the compound egg yolk ointment group and BNIP3 overexpression group,or between the model group and compound egg yolk ointment+BNIP3 silence group(both P>0.05).Conclusion Compound egg yolk ointment may activate mitochondri-al autophagy accelerate angiogenesis and granulation tissue generation through regulating BNIP3/NIX signaling pathway,thus to promote the healing of diabetic ulcer wound.关键词
糖尿病溃疡/复方蛋黄油膏/Bcl-2/腺病毒E1B 19kDa相互作用蛋白 3/NIP3 样蛋白X/线粒体自噬Key words
diabetic ulcer/compound egg yolk ointment/BNIP3/NIX/mitochondrial autophagy分类
医药卫生引用本文复制引用
谭谈,李维,杨明锦,苏俊檩..基于BNIP3/NIX信号通路介导的线粒体自噬探讨复方蛋黄油膏对糖尿病溃疡小鼠创面愈合的影响[J].现代中西医结合杂志,2025,34(8):1043-1049,7.基金项目
湖南省中医药管理局科研项目(D2024035) (D2024035)
湖南中医药大学院校联合基金项目(2024XYLH096) (2024XYLH096)
湖南省自然科学基金项目(2025JJ80435) (2025JJ80435)
常德市科技创新指导性项目(2024ZD69) (2024ZD69)