中国病理生理杂志2025,Vol.41Issue(2):338-347,10.DOI:10.3969/j.issn.1000-4718.2024.00.023
基于PINK1/parkin通路介导线粒体自噬探讨冲和膏促进糖尿病溃疡创面愈合的机制
Mechanism of Chonghe paste promoting wound healing of diabetic ulcer through PINK1/parkin pathway-mediated mitophagy
摘要
Abstract
AIM:To explore the mechanism of Chonghe paste in regulating PTEN-induced kinase 1(PINK1)/parkin pathway-mediated mitophagy on diabetic ulcer wound healing.METHODS:Thirty-six rats were used to construct a diabetic ulcer model by high-sugar and high-fat feed,intraperitoneal injection of streptozotocin and skin defect method,and were randomly divided into model group,Chonghe paste group and growth factor group,with 12 rats in each group.Another 12 rats were taken to construct normal wound model as normal group.The rats in normal group and model group were treated with normal saline for debridement,while those in Chonghe paste group and growth factor group were treated with Chonghe paste and growth factors for wound coating,respectively.The changes in fasting blood glucose and wound healing were observed and recorded,and samples were collected on the 7th and 14th days after treatment.The expression levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),P62 and collagen type Ⅲ(COL3)in granulation tissues were detected by immunohistochemistry.The mitochondrial ultrastructure was observed under an electron microscope,and the number of autophagosomes was recorded.The expression of PINK1,parkin and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)in wound tissues was detected by immunofluorescence,Western blot and RT-qPCR.RE-SULTS:Compared with normal group,the blood glucose levels of the rats in model group,Chonghe paste group and growth factor group were higher than 16.67 mmol/L on the 7th,14th and 28th days,indicating successful modeling of dia-betes.Compared with normal group,the rats in model group had a lower wound healing rate,the mean absorbance of IL-6,TNF-α and P62 was increased,the mean absorbance of COL3 was decreased,the number of autophagosomes per unit area was increased,the mean absorbance of PINK1,parkin and LC3-Ⅱ was decreased,and the mRNA and protein expres-sion levels of PINK1,parkin and LC3-Ⅱ were decreased.Compared with model group,the wound healing rate of the rats in Chonghe paste group and growth factor group was increased,the mean absorbance of IL-6,TNF-α and P62 was de-creased,the mean absorbance of COL3 was increased,the number of autophagosomes per unit area was decreased,the mean absorbance of PINK1,parkin and LC3-Ⅱ was increased,and the mRNA and protein expression levels of PINK1,parkin and LC3-Ⅱ were elevated.CONCLUSIONS:Chonghe paste can alleviate local inflammatory response in diabetic ulcer wounds,reduce the levels of inflammatory factors IL-6 and TNF-α,promote COL3 expression,activate the PINK1/parkin signaling pathway,and promote mitophagy in wounds,thus accelerating wound healing.关键词
冲和膏/糖尿病溃疡/创面愈合/线粒体自噬/PINK1/parkin信号通路Key words
Chonghe paste/diabetic ulcer/wound healing/mitophagy/PINK1/parkin signaling pathway分类
医药卫生引用本文复制引用
党赢,焦雨琦,海日,师建平..基于PINK1/parkin通路介导线粒体自噬探讨冲和膏促进糖尿病溃疡创面愈合的机制[J].中国病理生理杂志,2025,41(2):338-347,10.基金项目
国家自然科学基金资助项目(No.82460899) (No.82460899)
内蒙古自治区高等教育科学研究项目(No.NJZY23131) (No.NJZY23131)
内蒙古自治区草原英才团队滚动支持项目(No.CYYCTD2024017) (No.CYYCTD2024017)