ALA/LA Inhibited Renal Tubulointerstitial Fibrosis of DKD db/db Mice Induced by Oxidative Stress

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Its progression is caused by various pathological mechanisms, including oxidative stress (OS), inflammation, and fibrosis. This study aimed to explore the effects of alpha-linolenic acid (ALA)/ linoleic acid (LA) on preventing and delaying the progression of interstitial fibrosis and improving OS in DKD mice. Methods Male eight-week-old db/db mice were randomly allocated to either the DKD model group, the low-dose ALA/LA group (250 mg/kg·d), the high-dose ALA/LA group (500 mg/kg·d), or the control group, consisting of db/m mice. After 12 weeks of ALA/LA intervention, blood urea nitrogen, blood glucose, and urine protein levels were signifi-cantly lower in db/db mice than in the control group; Results ALA/LA enhanced SOD and CAT levels and reduced reactive oxygen species and MDA production. Furthermore, db/db mice in the intervention group had lower mRNA and protein expression levels of p38, p-p38, ERK, p-ERK, /transforming growth factor-β1 (TGF-β1), and type IV collagen (ColIV) than did the model group (P < 0.05); Conclusions ALA/LA improved recovery from injury in db/db mice by reducing OS and alleviating kidney fibrosis, especially in the tubules. The potential mechanism was that ALA/LA inhibited renal tubulointerstitial fibrosis and OS via the P-P38, P-ERK/ TGF-β1/ColIV signaling pathway.