Protective role of endogenous hydrogen sulfide in ischemic AKI by inhibiting NOD1 signal pathway

doi:10.3877/cma.j.issn.2095-3216.2017.02.006

Abstract

Abstract:

Objective

To observe whether restraining production of endogenous hydrogen sulfide in ischemic acute kidney injury can aggravate renal interstitial inflammation and cell apoptosis by activating NOD1 signal pathway.

Methods

Male Wistar rats were randomly divided into 4 groups: sham group, kidney ischemia/reperfusion (I/R) group, kidney ischemia/reperfusion (I/R) group + propargyl glycine (PAG) group, and kidney ischemia/reperfusion (I/R) group + hydroxyammonia (HA) group. Western blotting detected the kidney tissue NOD1, caspase-1, and NF-κB proteins; Real-time quantitative PCR detected NOD1 mRNA; Immunohistochemistry detected the kidney TNF-ɑ expression; HE staining observed pathological change in kidneys; and TUNEL detected kidney tissue cells apoptosis.

Results

Compared with the sham group, the I/R group kidneys showed significantly increased proteins expression of NOD1 (t=17.81, P=0.006), caspase-1 protein expressions (t=7.78, P=0.04), NF-κB (t=12.08, P=0.04), and TNF-ɑ (t=10.3, P=0.026); NOD1 mRNA expression also increased significantly (t=8.73, P=0.007); HE staining showed that the acute tubular necrosis, and renal tubular injury scores increased significantly (t=11.0, P=0.04); TUNEL dyeing showed that apoptotic cells increased significantly in ischemia zone (t=18.47, P=0.023). Compared with the I/R group, I/R+ PAG group showed significantly increased proteins expression of NOD1 (t=12.51, P=0.031), caspase-1 (t=8.81, P=0.024), NF-κB (t=5.88, P=0.02), and TNF-ɑ (t=11.04, P=0.04); NOD1 mRNA expression increased significantly (t=8.11, P=0.001); HE staining showed that the acute tubular necrosis and renal tubular injury scores increased significantly (t=13, P=0.03); TUNEL dyeing showed that apoptotic cells increased significantly in ischemia zone (t=16.41, P=0.04). I/R + HA group also showed significantly increased proteins expression of NOD1 (t=13.35, P=0.006), caspase-1 (t=9.4, P=0.011), NF-κB (t=5.27, P=0.01), and TNF-ɑ (t=4.98, P=0.033); NOD1 mRNA expression was increased significantly (t=8.94, P=0.02); HE staining showed that the acute tubular necrosis and renal tubular injury scores increased significantly (t=13, P=0.03); TUNEL dyeing showed that apoptotic cells increased significantly in ischemia zone (t=10.77, P=0.031).

Conclusion

Inhibition of hydrogen sulfide activated NOD1-like receptor-dependent inflammatory pathway, so as to aggravate the renal ischemia/reperfusion injury.

Key words: Hydrogen sulfide, Ischemia reperfusion, NOD1 receptor

Jiali Wang, Guangyuan Li, Lina Mu, Zhe Zhang, Wenli Liu, Junxia Wang, Fang Ma, Zhicheng Tan. Protective role of endogenous hydrogen sulfide in ischemic AKI by inhibiting NOD1 signal pathway[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2017, 06(02): 73-78.

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Figures/Tables 5

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