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Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent*
Objective: Despite extensive research, the mortality rate of patients with sepsis-induced acute kidney injury (AKI) is unacceptably high, especially in the elderly. Current sepsis models have difficulties in reproducing AKI. This study aimed to develop a novel, clinically relevant mouse model for sepsis-induced AKI by uterine ligation and inoculation of bacteria. In addition, the age dependency of the severity of sepsis and sepsis-induced AKI was studied by validating this model in three different age categories.
Design: Experimental animal investigation.
Setting: University research laboratory.
Subjects: Young (12–14 wks), aged (46–48 wks), and old (70–72 wks) C57BL/6 female mice were used as models for adolescent, adult premenopausal, and elderly postmenopausal women, respectively.
Interventions: Uterine ligation and inoculation with 103 colony forming unit Escherichia coli or saline (sham) was performed; in vivo imaging with a luminescent Escherichia coli strain documented the course of infection.
Measurements and Main Results: All mice had established Escherichia coli sepsis at 48 hrs postinfection, with higher mortality rate in old (43%) compared to aged (23%) or young (9%) mice. Infected mice had elevated serum or plasma cytokine, chemokine (tumor necrosis factor, interleukin-6, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and interleukin-10), and NOx− concentrations compared to sham mice. AKI was confirmed by renal histology. Serum creatinine concentrations at 48 hrs increased with age (mean ± sem; controls 0.18 ± 0.03 mg/dL, young 0.28 ± 0.03 mg/dL, aged 0.38 ± 0.05 mg/dL, and old 0.44 ± 0.06 mg/dL).
Conclusion: The uterine ligation and inoculation model for sepsis-induced AKI starts from a real infectious focus and shows an age-dependent severity of septic AKI that resembles AKI in humans.
出处:(Crit Care Med 2012; 40:2638–2646)
Key Words: acute kidney injury; ageing; in vivo imaging; mouse; sepsis; uterus
Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent*
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