Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in d-galactose-induced aging rats`

Background: Recently, the d-galactose (d-gal)-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic d-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in d-galinduced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis. Objective: To investigate the acute kidney injury (AKI) and inflammatory response of sepsis following cecal ligation and puncture (CLP) in d-gal-induced aging rats. Methods: Twelve-week-old male Sprague Dawley rats were divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500 mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6 weeks, the CLP method was used to establish a sepsis model. Results: The mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-a were markedly increased in the H d-gal group after establishment of the sepsis model (H d-gal vs control, P < 0.05 at 12 h and 24 h post-CLP). The rate of severe AKI (RIFLE-F) at 24 h post-CLP was 43% for both the control and L d-gal groups and 80% for the H d-gal group. Conclusion: High-dose-d-gal-induced aging rats are more likely to die from sepsis than are young rats, and probably this is associated with increased severity of septic AKI and an increased inflammatory response. Therefore, use of the high-dose-d-gal-induced aging rat model of sepsis for preclinical studies can provide more useful information for the treatment of sepsis in elderly patients.