Abstract
Purpose To explore the effect of milk fat globule-epidermal growth factor 8 (MFG-E8) on sepsis-induced acute kidney injury (SAKI). MethodsMale C57BL/6 mice were randomized to control, sham, CLP, CLP+PBS, and CLP+rmMFG-E8 groups. SAKI was induced by cecal ligation and puncture (CLP). Recombinant mouse MFG-E8 (rmMFG-E8) (20 μg/kg) or PBS (vehicle) was administered intraperitoneally. Blood, urine and renal tissue were collected at 24 h after CLP. Blood samples were tested for serum kidney injury biomarker and cytokines. Urine samples were collected to detect KIM-1, and NGAL. Real-time PCR was tested for Bax and Bcl-2. TUNEL staining was used to determine renal apoptosis. Western blot was used to detect the expression of Bax, Bcl-2, and proteins in the NF-κB pathway. Results MFG-E8 alleviated SAKI by decreasing serum Cre, BUN, urine KIM-1 and NGAL and by mitigating renal pathological changes significant (p < 0.05). IL-1β, IL-6, TNF-α were significantly inhibited by MFG-E8 (p < 0.05). Apoptosis induced by SAKI was markedly suppressed by MFG-E8. Finally, MFG-E8 attenuated the activation of the NF-𝜅B signaling pathway in SAKI. ConclusionMFG-E8 has beneficial effects on SAKI, which may be achieved by inhibiting the NF-κB pathway.
Highlights
Acute kidney injury (AKI) is one of the most common and severe complications of sepsis1; 40-50% of patients with sepsis develop AKI with a 6 to 8 folds increase in mortality[2]
Urine NGAL and kidney injury molecule-1 (KIM-1) can be used as early biomarkers of AKI
The results showed that urinary NGAL and KIM-1 levels were significantly elevated in the cecal ligation and puncture (CLP) and CLP + PBS groups; rmMFG-E8 significantly reduced urinary NGAL and KIM-1 levels (Fig. 1 C, D)
Summary
Acute kidney injury (AKI) is one of the most common and severe complications of sepsis1; 40-50% of patients with sepsis develop AKI with a 6 to 8 folds increase in mortality[2]. Sepsis-induced AKI leads to the accumulation of various metabolites and further causes severe clinical consequences. AKI carries a two-fold increased risk of end-stage chronic kidney disease within five years[5]. Sepsis-induced AKI causes a substantial financial burden[7]. AKI increases the durations of mechanical ventilation and hospital stays[8]. These urgently require us to understand the pathogenesis of AKI in sepsis and to carry out early treatment
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