光甘草定通过调控铁死亡通路改善糖尿病视网膜病变大鼠的铁代谢紊乱与视网膜损伤OA

Objective To investigate the effects of glabridin(Gla)on iron metabolism and ferroptosis pathways in rats with diabetic retinopathy(DR).Methods Rats were randomly divided into the Con group,DR group,10-Gla group,20-Gla group,40-Gla group,and 40-Gla+10-Erastin group,with 12 rats in each group.Rats in the DR group,10-Gla group,20-Gla group,40-Gla group,and 40-Gla+10-Erastin group were intraperitoneally injected with a single dose of 65 mg·kg-1 streptozotocin to induce the DR model,while rats in the Con group served as controls.Rats in the Con and DR groups were intragastrically administered 5 g·L-1 carboxymethylcellulose sodium.Rats in the 10-Gla,20-Gla,and 40-Gla groups received intragastric Gla solution at doses of 10,20,and 40 mg·kg-1·d-1,respectively.Rats in the 40-Gla+10-Erastin group were given intragastric Gla(40 mg·kg-1·d-1)solution combined with tail vein injection of Erastin(a ferroptosis inducer,10 mg·kg-1·d-1).All interventions lasted for 4 weeks.Fasting plasma glucose(FPG)levels were measured using a blood glucose meter,and glycated hemoglobin(HbA1c)levels were detected by the enzyme-linked immunosorbent assay.Hema-toxylin-eosin staining and periodic acid-Schiff staining were used to observe retinal morphology and angiogenesis.Retinal malondialdehyde(MDA)levels were determined by the thiobarbituric acid method.Reduced glutathione(GSH)and Fe2+levels were detected by the micromethod.Retinal 4-hydroxynonenal(4-HNE)levels were measured by the enzyme-linked immunosorbent assay.Quantitative real-time polymerase chain reaction was performed to measure the mRNA levels of reti-nal ferritin heavy chain 1(FTH1),ferroportin 1(FPN1),transferrin receptor(TFRC),glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A1 1),acyl-CoA synthetase long-chain family member 4(ACSL4),nicotinamide ade-nine dinucleotide phosphate oxidase 4(NOX4),tumor protein p5 3(p53),prostaglandin-endoperoxide synthase 2(PTGS2),and ferritin.Western blot was used to detect retinal GPX4 protein expression.Results Compared with the DR group,the 10-Gla,20-Gla,and 40-Gla groups showed decreased FPG and HbA1c levels,alleviated retinal injury and angiogenesis,in-creased retinal ganglion cell(RGC)count,reduced neovascular branch number,lowered MDA and 4-HNE levels,elevated GSH levels,decreased Fe2+content,upregulated mRNA levels of FTH1 and FPN1,downregulated mRNA levels of TFRC and ferritin,increased mRNA levels of GPX4 and SLC7A11 as well as GPX4 protein expression,and reduced mRNA levels of PTGS2,ACSL4,NOX4,and p53(all P＜0.05).Compared with the 40-Gla group,the 40-Gla+10-Erastin group exhibited in-creased FPG and HbA1c levels,aggravated retinal injury and angiogenesis,decreased RGC count,elevated neovascular branch number,higher MDA and 4-HNE levels,lower GSH levels,increased Fe2+content,downregulated mRNA levels of FTH1 and FPN1,upregulated mRNA levels of TFRC and ferritin,decreased mRNA levels of GPX4 and SLC7A11 as well as GPX4 protein expression,and elevated mRNA levels of PTGS2,ACSL4,NOX4,and p53(all P＜0.05).Conclusion Gla can alleviate retinal damage,oxidative stress,and iron metabolism disorder in DR rats by inhibiting ferroptosis.