Mechanism by which 24-week different-volume high-intensity interval training ameliorates renal fibrosis in naturally...

To investigate the effects of 24-week different-volume high-intensity interval training (HIIT) on renal fibrosis in naturally aging rats and to elucidate the underlying mechanisms based on the TGF-β1/Smad signaling pathway.

Forty 12-month-old male Wistar rats were randomly divided into a baseline control group (Group B, n = 10), a natural aging control group (Group C, n = 10), a high-volume HIIT group (Group H1, 25-min, n = 10), and a low-volume HIIT group (Group H2, 15-min, n = 10). Group B was sacrificed at the beginning of the experiment. Group C was fed without exercise for 24 weeks. Groups H1 and H2 underwent treadmill training with corresponding volumes (3 days/week for 24 weeks). An incremental volume test was conducted every 4 weeks to adjust exercise intensity. Body weight, blood, and urine indicators were monitored every 4 weeks. ELISA was used to measure 24-h urinary protein, serum creatinine, and creatinine clearance rate in each group. Body composition was monitored using DEXA every 8 weeks. After the intervention, renal tissues were collected. Pathological morphology and fibrosis degree were observed via HE and Masson staining. The gene and protein expression of TGF-β1, Smad2, Smad3, and p-Smad2/3 in the kidneys were detected using qPCR and Western blot.

Compared with Group C, both HIIT groups effectively inhibited the age-related increase in body fat percentage and loss of lean body mass (P < 0.05), significantly reduced 24-h urinary protein levels, maintained stable serum creatinine, and increased creatinine clearance rate (P < 0.05). Histological results showed that renal pathological damage was reduced in both HIIT groups, and the collagen volume fraction (CVF) was significantly lower than in Group C (P < 0.01). Molecular mechanism studies revealed that the expression of key molecules in the TGF-β1/Smad pathway was significantly higher in Group C than in Group B (P < 0.05). In contrast, HIIT intervention significantly suppressed the activation of this pathway, with Group H1 showing more comprehensive effects in reducing the protein expression of TGF-β1, Smad2/3, and p-Smad2/3.

24-week HIIT intervention can effectively delay the decline of renal function and the progression of renal fibrosis in naturally aging rats. Its protective effect may be associated with inhibiting the overactivation of the TGF-β1/Smad signaling pathway. High-volume HIIT (H1) induced a more profound suppression of the pro-fibrotic pathway, whereas low-volume HIIT (H2) represents a time-efficient strategy conferring notable protection at the phenotypic level.