肤痔清软膏调控铁死亡改善糖尿病足溃疡的机制研究OA

Objective In order to elucidate the therapeutic effect of Fuzhiqing ointment on mouse models of diabetic foot ulceration(DFU)and its impact on ferroptosis activity in ulcer models.Methods C57BL/6 male mice were randomly divided into control group,model group,Fuzhiqing ointment group(short for FZQ group)and FZQ+ferroptosis inducing agent(Erastin)group(short for FZQ+Erastin group)using a randomized block method.Except for the control group,mice in other groups were induced with diabetes by streptozotocin,and then underwent back skin excision to establish the DFU model.Then Fuzhiqing ointment was applied to the wound or combined with intraperitoneal injection of Erastin for intervention.The body weight,blood glucose and wound healing of mice were recorded on days 1,3,7,14 and 21 after modeling.The pathological changes of skin tissue were detected by hematoxylin-eosin(HE)staining,and the levels of Fe2+,malondialdehyde(MDA)and lipid peroxidation(LPO)in skin tissue were detected by kits.Western blotting was used to detect the expression levels of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11)and heme oxygenase 1(HMOX1)in skin tissue.Results Compared with the control group,the body weight of the mice in the model group decreased significantly,while the blood glucose level increased significantly,and the healing effect became slow.At the same time,disordered arrangement of fibroblasts and massive inflammatory cells infiltration were observed in the skin tissue of the model group.After Fuzhiqing ointment treatment,the symptoms of DFU mice were significantly improved.Mechanistically,compared with the control group,the levels of MDA,LPO,Fe2+and the expression of HMOX1 in the model group were significantly increased,while the expressions of GPX4 and SLC7A11 were inhibited.Fuzhiqing ointment inhibited the increasing of ferroptosis activity in the model group.However,Erastin treatment attenuated the therapeutic effect of Fuzhiqing ointment on DFU and partially reversed its inhibitory effect on ferroptosis.Conclusion Fuzhiqing ointment can effectively improve the symptoms of DFU in mice,and its therapeutic mechanism may be related to the regulation of ferroptosis activity.