中药新药与临床药理2025，Vol.36Issue(2)：243-250,8.DOI:10.19378/j.issn.1003-9783.2025.02.010
基于蛋白组学探讨冲和膏调控血管内皮生长因子通路促进糖尿病溃疡大鼠创面愈合的作用机制
Exploration on the Mechanism of Chonghe Ointment in Regulating VEGF Pathway to Promote Wound Healing in Diabetes Ulcer Rats Based on Proteomics
摘要
Abstract
Objective To explore the mechanism of Chonghe Ointment in regulating vascular endothelial growth factor(VEGF)pathway to promote wound healing in diabetes ulcer rats based on proteomics.Methods A rat model of diabetes ulcer was established by the method of feeding high-sugar high-fat diet+intraperitoneal injection of streptozotocin(STZ)+skin defect.SD rats were randomly divided into blank group,model group,Chonghe Ointment group and growth factor group,with six rats in each group.The rats in Chonghe Ointment group were applied with Chonghe Ointment once a day for successively 14 days.Masson staining was used to observe the growth of collagen fibers in the granulation tissues of wounds.Immunohistochemistry was used to detect the expression changes of CD34 and VEGF in the granulation tissues.Differentially expressed proteins between model group and Chonghe Ointment group were detected by proteomics.GO functional enrichment analysis was performed using the DAVID platform and metabolic pathway enrichment analysis were conducted using the KEGG database.Western Blot was used to detect the expression levels of VEGF-related protein in the granulation tissues of wounds.Results Compared with the blank group,the distribution of collagen fibers in the model group was sparse and disordered,less blue stained collagen fibers were seen and the proportion of collagen fiber area was significantly reduced(P<0.05).The number of CD34 labeled blood vessels was relatively small,the diameter was thin,and the microvascular density(MVD)value,and VEGF positive expression were significantly down-regulated(P<0.05,P<0.01).The protein expression of Pxn,Casp9,Nos3 and Ptk2 were significantly up-regulated(P<0.01).The VEGF protein expression was significantly down-regulated(P<0.01).Compared with the model group,the collagen fibers in the Chonghe Ointment group and the growth factor group were arranged neatly and orderly,with more deposition of blue stained collagen fibers.The proportion of collagen fiber area was significantly increased(P<0.01).The number of CD34 labeled blood vessels was relatively large,the diameter was thick,MVD value and VEGF positive expression were significantly up-regulated(P<0.01).The protein expression of Pxn,Casp9,Nos3 and Ptk2 were significantly down-regulated(P<0.01).The VEGF protein expression was significantly up-regulated(P<0.01).Compared with the model group,a total of 221 differentially expressed proteins were screened in Chonghe Ointment group,including 28 up-regulated proteins and 193 down-regulated proteins,which mainly involve in multiple signaling pathways such as cytoskeleton tissue,supramolecular fibrous tissue,actin cytoskeleton tissue,VEGF,insulin resistance,PI3K-Akt,etc.Conclusion Chonghe Ointment can promote wound healing in diabetes ulcer rats.Its possible mechanism is related to promoting the formation and angiogenesis of collagen fibers in granulation tissues and regulating the VEGF signaling pathway.关键词
冲和膏/糖尿病溃疡/蛋白组学/血管内皮生长因子通路/胶原纤维/血管新生/大鼠Key words
Chonghe Ointment/diabetes ulcer/proteomics/VEGF pathway/collagen fibers/angiogenesis/rats分类
医药卫生引用本文复制引用
党赢,张锁,董重阳,海日,吴昊,白洁,陈旭,焦雨琦,师建平..基于蛋白组学探讨冲和膏调控血管内皮生长因子通路促进糖尿病溃疡大鼠创面愈合的作用机制[J].中药新药与临床药理,2025,36(2):243-250,8.基金项目
国家自然科学基金地区项目(82460899) （82460899）
内蒙古自治区高等教育科学研究项目(NJZY23131) （NJZY23131）
内蒙古自治区草原英才团队滚动支持项目(CYYCTD2024017). （CYYCTD2024017）
