高脂饮食大鼠耳廓痤疮模型的铁死亡实验研究OA

Objective To establish an acne model on rat auricles co-induced by a high-fat diet and Propionibacterium acnes(P.acnes)to investigate the role of ferroptosis in acne pathogenesis,exploring whether a high-fat diet exacerbates acne-like tissue damage by influencing ferroptosis.Methods Six-week-old male SPF SD rats were randomly assigned to control,acne,and high-fat diet(HFD)acne groups(n=10).The control and acne groups were fed a low-fat diet for 12 weeks,while the HFD acne group was fed a high-fat diet providing 45%of energy from fat in the same duration for 12 weeks.Subsequently,an auricular acne model was established through intradermal P.acnes injection combined with topical oleic acid.Right auricle thickness and mass were measured after 12 weeks,along with serum ROS,testosterone(T),and estradiol(E2)levels.Auricle tissue histopathological features and mitochondrial ultrastructural changes were analyzed using HE staining and transmission electron microscopy.The relative expression levels of GPX4,xCT,FSP1 and TFR1 were detected by q-PCR and Western Blot.Results The body mass,ear thickness,and ear mass of rats in the HFD acne group were significantly increased compared with those in the control and acne groups(P＜0.01,P＜0.001,P＜0.000 1).Serum levels of ROS and T were elevated in the HFD acne group(P＜0.05).E2 levels were significantly reduced in the HFD acne and acne groups(P＜0.000 1).mRNA and protein expression of GPX4,xCT,and FSP1 in auricular tissue were downregulated in the HFD acne and acne groups(P＜0.01),while TFR1 expression was upregulated(P＜0.05).HE staining revealed substantial neutrophil accumulation in the stratum corneum of model rats,along with significant thickening of the epidermis and prickle cell layer.In the dermis,the number of sebaceous glands and hair follicles was reduced,accompanied by extensive inflammatory cell infiltration.Epidermal thickness and sebaceous gland diameter were significantly increased in the model rats(P＜0.05 or P＜0.01);these pathological alterations were more pronounced in the HFD acne group compared with the acne group.Ultrastructural mitochondria examination showed characteristics indicative of ferroptosis,including reduced volume,condensed membranes,and loss of cristae.Conclusions This study establishes ferroptosis as a important player in acne pathogenesis.A high-fat diet may promote acne progression by systematically inducing hormonal imbalances,disrupting metabolic homeostasis,and exacerbating oxidative stress,regulating ferroptosis.These findings provide a novel theoretical basis for clinical interventions targeting obesity-related acne.