阿魏酸抗糖尿病大鼠骨髓氧化应激对循环内皮祖细胞的影响OA

Objective To investigate the effect of ferulic acid(FA)on circulating endothelial progenitor cells(EPCs)by alleviating bone marrow oxidative stress in anti-diabetic rats.Methods After 4 weeks of high-fat diet feeding,three-week-old male Sprague-Dawley rats were administered streptozotocin(STZ)via intraperitoneal injection for induction of type 2 diabetes.Full-thickness skin measuring about 2 cm in diameter was removed on both sides of the rat spine to create a model of a skin ulcer.After successful modeling,the rats were randomly divided into an FA group and a model group.Rats in the normal group underwent the same skin ulcer modeling,while the high-fat diet feeding and STZ injection were excluded.All groups received intraperitoneal injections,the FA group was treated with FA at a dose of 30 mg/kg,and the other groups were administered an equal volume of physiological saline.Flow cytometry was used to assess reactive oxygen species(ROS)levels and EPCs counts in bone marrow and peripheral blood.Enzyme-linked immunosorbent assay(ELISA)was used to measure endothelial nitric oxide synthase(eNOS)in bone marrow,stromal cell-derived factor-1α(SDF-1α)and CXC chemokine receptor 4(CXCR4)levels in bone marrow,serum,and wound tissues.The nitric oxide(NO)level in bone marrow was determined by the nitrate reductase method.Results Compared with the normal group,the model group exhibited significantly increase in ROS levels in both bone marrow and peripheral blood(P<0.05),while the expressions of SDF-1α and CXCR4 in the bone marrow,serum,and wound tissue,along with the levels of eNOS and NO in the bone marrow,were all significantly decreased(P<0.05),as well as reduced EPCs counts in bone marrow and peripheral blood(P<0.05).Compared with the model group,the FA group showed significantly lower ROS levels in bone marrow and peripheral blood(P<0.05),increased expression of SDF-1α and CXCR4 in bone marrow,serum,and wound tissues,and significantly increased eNOS and NO levels in bone marrow(P<0.05),along with a significantly increased in EPCs numbers in both bone marrow and peripheral blood(P<0.05).Conclusion Hyperglycemia can induce oxidative stress in the bone marrow,and increase the stress injury,suppress the SDF-1α/CXCR4 axis and eNOS/NO pathway,thereby impairing EPCs mobilization into the peripheral circulation.FA intervention can reverse this process and promote EPCs mobilization into the bloodstream.