Lactobacillus rhamnosus CMU-pb-7 Alleviates Diabetic Nephropathy in a High-Fat Diet-Streptozotocin Rat Model

Background Lactobacillus rhamnosus CMU-pb-7, one of the normal intestinal floras, can regulate intestinal micro-ecology and improve the body's anti-oxidative stress function, yet its protective role in diabetic nephropathy (DN) remains unclear. Methods 24 male rats were divided into a normal control, a DN model, and a CMU-pb-7 treatment group. The DN model was induced by a high-fat diet plus streptozotocin. After CMU-pb-7 administration, biochemical and oxidative stress indicators and renal histopathology was detected. Renal Keap1, Nrf2, HO-1, and Gpx4 expression was determined by IHC, RT-PCR, and Western Blot. In vitro, AGEs-stimulated HK-2 cells were treated with butyrate, and cell viability, ROS level, and the related protein expression were determined. Results Compared with the DN model group, CMU-pb-7 treatment significantly improved the general condition and serum biochemical profiles of DN rats, with reductions in serum TC, TG, UA, SCr and BUN (36.30%, 55.10%, 36.00%, 39.70%, 60.60%). CMU-pb-7 also effectively reversed DN-related renal interstitial fibrosis, restored renal antioxidant capacity by increasing GSH and SOD levels (58.30%, 99.80%), and reduced MDA and Fe²⁺ levels (38.10%, 24.30%). IHC, qPCR, and Western blot analyses showed a suppressed expression of Nrf2, HO-1, and Gpx4, concomitantly with an elevation in Keap1 in DN rat kidney tissues. These alterations were effectively reversed by CMU-pb-7 administration. In HK-2 cells, butyrate treatment significantly attenuated AGEs-induced increased ROS levels and the downregulation of Nrf2/HO-1/Gpx4 pathway. Conclusion CMU-pb-7 alleviates renal dysfunction in DN rats, possibly by reducing oxidative stress, an effect associated with activation of the renal Nrf2/HO-1/Gpx4 pathway.