The effect and mechanism of lipoic acid on diabetic nephropathy in type 1 diabetic rats

WANG Xing; LONG Dongmei; GUO Nan

doi:10.13506/j.cnki.jpr.2025.03.003

Abstract：Objective To study the effect of lipoic acid(ALA)on type 1 diabetic nephropathy(DN)rats and explore its mechanism.Methods After successfully inducing type 1 DN in SD rats with STZ,the model rats were randomly divided into model group and ALA(100 mg·kg-1)treatment group,and another 10 normal SD rats of the same age were taken as normal control group and given orally ALA for 12 weeks.During the experiment,the body weights of the rats,random blood glucose,fasting blood glucose,glycosylated hemoglobin,food intake and water consumption were measured,the oral glucose tolerance test was carried out,and the urine was collected with metabolic cage.After the rats were killed,the serum and kid-neys were taken.The indexes related to renal diseases in serum and urine were measured,and the indexes related to lipid metabolism,oxidative stress and inflammatory reaction in serum were detected.The related indexes of oxidative stress and protein expression in kidney were examined.Results ALA had no effect on the basic metabolic indexes in diabetic ne-phropathy rats,but it can attenuate the abnormal glucose tolerance.ALA significantly reduced the urine volume,the levels of urine glucose,urinary microalbumin,β2 microglobulin and ACR index in diabetic nephropathy rats,and inhibited the activity of N-acetylglucosaminidase.ALA decreased the contents of creatinine,blood urea nitrogen in serum,the renal index,and markedly alleviated renal pathological abnormalities in diabetic nephropathy rats.ALA relieved the dyslipidemia,en-hanced the activities of antioxidant enzymes in serum and kidney,reduced the content of malondialdehyde(MDA),noticea-bly reduced the levels of proinflammatory factors and increased the content of anti-inflammatory factors in serum.ALA up-regulated the expression of protein nuclear factor E2 related factors(Nrf2)and heme oxygenase-1(HO-1),and inhibited the expression of protein kelch-like ECH-associated protein-1(Keap1)and phosphorylated nuclear factor-kappaB(NF-κB)in kidney of the diabetic rats.Conclusion ALA may regulate the Nrf2/Keap1 and NF-κB signaling pathway,thus in-hibiting the oxidative stress damage and inflammatory reaction in kidney of the diabetic rats,and further improving type 1 DN.