| Objective:To investigate whether the inhibition of oxidative stress by NADPH inhibitor in ischemia/reperfusion injury(IRI)of the kidney could be alleviated by the nucleotide-binding oligomerization domain-2(NOD2)signaling pathway.Methods:Twenty-four male Wistar rats were randomly divided into four groups after the right kidney was removed:(1)Sham group: the left renal pedicle was isolated and not clamped,and kidney tissue samples were taken 24 hours later.(2)Renal ischemia-reperfusion(IRI)group: After separation of the left renal pedicle,the left renal artery was clamped without damage to the arterial clamp for 45 minutes,and renal tissue samples were taken 24 hours after reperfusion.(3)IRI group + 4-hydroxy-3 methoxyacetophenone(Apocynin)group:continuous injection of Apocynin in the left renal artery for 10 min(concentration: 10 ?mol / min),discontinuation After 3 minutes,the left renal pedicle of the rat was clamped with a non-invasive arterial clip,and the block was released after 45 minutes to prepare a kidney IRI model.(4)IRI group + diphenylene iodonium(DPI)group: DPI was continuously injected into the left renal artery for 10 min(concentration: 1 ?mol / min),and the kidney IRI model was established in the same manner as above after 3 min of withdrawal;Group and IRI group were injected with the same amount of saline in the left renal artery.Twenty-four hours after the end of the experiment,rat kidney tissue specimens of each group were collected,and the expression of NOD2,nuclear factor-?B(NF-?B),and cysteine protease(Caspase-1)proteins were measured by Western blot.Detection;RT-PCR was used to detect the expression of NOD2 mRNA;renal pathological changes were observed by HE staining;renal tissue inflammatory factor interleukin-1?(IL-1?)expression was detected using immunohistochemistry.Results:(1)Compared with the Sham group,the expression of NOD2,NF-? B,and Caspase-1 protein in the kidney tissue of rats in the IRI group was significantly increased(P <0.05);the expression of NOD2 mRNA was significantly increased(P <0.05);The expression of tissue inflammatory factor IL-1? was significantly increased(P <0.05).The pathological manifestations of renal tissue in group IRI were acute tubular necrosis,damaged epithelial cells blocked the renal tubules,a large number of inflammatory cells infiltrated in the interstitium,and the renal tissue pathological injury score increased significantly(P <0.05).(2)Compared with the IRI group,the expression of NOD2,NF-?B,and Caspase-1in the IRI + Apocynin group and the IRI + DPI group were significantly reduced(P<0.05);NOD2 mRNA expression was significantly reduced(P <0.05);IL-1? expression in rat kidney tissues was significantly reduced(P <0.05);pathology of renal tissue showed that the degree of acute tubular necrosis was reduced,and the renal tubular injury score was significantly reduced(P <0.05).Conclusion:(1)In renal ischemia-reperfusion injury in rats,NOD2 signaling pathway-mediated inflammatory pathways can be activated leading to acute kidney injury.(2)Inhibition of oxidative stress by NADPH oxidase inhibitors can block NOD2-like receptor-dependent inflammatory pathways to reduce renal IRI. |
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