To investigate the protective effect and mechanism of N-acetylcysteine (NAC) on acute kidney injury (AKI) in septic mice.

Sixty mice were divided into a sham operation group (sham group), a septic AKI group (SAKI group) and a SAKI + NAC group, with 20 mice in each group. The SAKI mouse model was constructed by cecal ligation and puncture (CLP), and mice in the SAKI + NAC group were performed CLP after pretreatment with NAC (50 mg / kg) for 3 d. Mice in the sham group only underwent surgery without CLP. All mice were sacrificed when the model was successfully constructed for 24 h, and the renal tissue pathological injury was evaluated by hematoxylin-eosin (HE) staining. The serum creatinine, blood urea nitrogen, tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6, pathological score, malondialdehyde, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and renal tissue apoptosis were compared among these three groups, as well as protein levels of Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), Caspase-3 and Bax.

HE staining showed that the glomerular, tubular and vascular structures were clear and normal in the renal tissue sections of mice in the sham group. The glomerular rupture, extensive tubular necrosis, loss of brush border and a large number of interstitial inflammatory cells were seen in the SAKI group. The renal tissue damage was alleviated, the glomerular and renal tubular epithelial cells revealed hyperemia and edema, and the interstitial inflammatory cells significantly decreased in the SAKI + NAC group. The serum creatinine [(39.0 ± 1.8), (129.6 ± 4.8), (81.7 ± 2.0) μmol / L], blood urea nitrogen [(6.65 ± 0.29), (24.78 ± 0.71), (15.45 ± 0.40) mmol / L], TNF-α [(16.8 ± 0.4), (43.5 ± 1.0), (22.0 ± 0.6) ng / L], IL-1β [(15.2 ± 0.7), (44.8 ± 1.0), (25.5 ± 0.8) ng / L], IL-6 [(20.8 ± 0.4), (70.6 ± 2.0), (35.8 ± 1.2) ng / L], pathological score [(0.65 ± 0.11), (3.55 ± 0.14), (2.00 ± 0.15)], malondialdehyde [(25.1 ± 0.7), (85.3 ± 1.1), (40.1 ± 1.6) nmol / g], SOD [(90.4 ± 1.4), (22.4 ± 0.8), (70.7 ± 2.5) U / mg], GSH-Px [(336.2 ± 5.5), (181.1 ± 2.5), (265.0 ± 6.4) U / mg], catalase [(14.9 ± 0.6), (5.7 ± 0.4), (8.4 ± 0.4) U / mg], TUNEL positive cells [(1.35 ± 0.20), (13.55 ± 0.72), (8.25 ± 0.42) cells], TLR4 protein [(0.14 ± 0.03), (0.40 ± 0.03), (0.18 ± 0.03)], NF-κB protein [(0.20 ± 0.04), (0.66 ± 0.05), (0.16 ± 0.03)], Caspase-3 protein [(0.152 ± 0.027), (0.464 ± 0.061), (0.147 ± 0.022)] and Bax protein [(0.14 ± 0.03), (0.71 ± 0.03), (0.15 ± 0.04)] levels were statistically significantly different in the sham group, SAKI group and SAKI + NAC group (F = 204.316, 328.913, 378.460, 327.102, 344.226, 123.104, 709.235, 421.732, 233.016, 104.521, 153.920, 127.135, 260.514, 115.960, 505.826; all P < 0.001). Further comparisons revealed that the serum creatinine, blood urea nitrogen, TNF-α, IL-1β, IL-6, pathological score, maldialdehyde, TUNEL positive cells and protein levels of TLR4, NF-κB, Caspase-3 and Bax were significantly lower in the SAKI + NAC group than in the SAKI group, and the SOD, GSH-Px and catalase levels were significantly higher (all P < 0.05).

NAC has a significant protective effect on AKI in septic mice, and its specific mechanisms are related to the inhibition of renal cell inflammation, anti-oxidative damage and anti-apoptosis.