NOD-like receptors can promote inflammation, and apocynin and diphenylene iodonium (DPI) are both oxidase inhibitors. The aim of this study was to investigate whether inhibition of oxidative stress in ischemic acute kidney injury could attenuate renal interstitial inflammatory responses and apoptosis through the NOD1 signaling pathway.

Male Wistar rats were randomly divided into 4 groups: sham operation group, renal ischemia-reperfusion (I/R) group, I/R+ apocynin group, and I/R+ DPI group. Western blotting was used to detect the renal protein expression of nucleotide-binding oligomeric domain like receptor 1 (NOD1), caspase-1, and nuclear factor-κB (NF-κB). Real-time quantitative PCR was used to detect NOD1 mRNA. The histological changes of the kidney were observed by HE staining. The expression of tumor necrosis factor-ɑ (TNF-ɑ) in renal tissue was detected by immunohistochemistry. The apoptosis of renal cells was detected by TUNEL method. Statistical analysis of experimental data was made with the SPSS 22.0 statistical soft pack.

Compared with the sham group, the I/R group had higher protein expression of NOD1, caspase-1, NF-κB, and TNF-ɑ in the kidney (t=16.81, t=7.28, t=11.08, t=10.11; P<0.05), as well as higher mRNA expression of NOD1 (t=-7.93, P<0.05); HE staining showed renal lesions of acute tubular necrosis, and the renal tubular injury score increased significantly (t=-11.0, P<0.05); TUNEL staining showed that apoptotic cells increased significantly in the renal ischemia zone (t=-18.38, P<0.05). Compared with the I/R group, the I/R+ apocynin group had lower protein expression of NOD1, caspase-1, NF-κB, and TNF-ɑ in the kidney (t=-10.9, t=-7.6, t=-4.9, t=-9.7; P<0.05), as well as lower mRNA expression of NOD1 (t=8.49, P<0.05); HE staining showed lower renal lesions of acute tubular necrosis, and the renal tubular injury score reduced significantly (t=-12, P<0.05); TUNEL staining showed that apoptotic cells reduced significantly in the renal ischemia zone (t=-11.3, P<0.05). Compared with the I/R group, the I/R+ DPI group had lower protein expression of NOD1, caspase-1, NF-κB, and TNF-ɑ in the kidney (t=-11.4, t=-6.8, t=-5.4, t=-10.6, P<0.05), as well as lower mRNA expression of NOD1 (t=7.5, P<0.05); HE staining showed lower renal lesions of acute tubular necrosis, and the renal tubular injury score reduced significantly (t=-11, P<0.05); TUNEL staining showed that apoptotic cells reduced significantly in the renal ischemia zone (t=-10.8, P<0.05).

Inhibition of oxidative stress might block NOD1-like receptor-dependent inflammatory pathways and cellular apoptosis, thereby reducing the renal ischemia-reperfusion injury.