Effect of Hydrogen Sulfide on Kidney Injury Induced by Urinary-Derived Sepsis / 天津医药

ABSTRACT

Objective To investigate the effect and mechanism of hydrogen sulfide (H2S) on kidney injury induced by urinary-derived sepsis. Methods Rabbits were randomly divided into Control group, Sham group, Sepsis group, NaHS 2.8μmol/kg group and NaHS 8.4μmol/kg group. Upper urinary tract obstruction and acute infection was induced to estab-lish Sepsis model. At 24 h before surgery, and 24 h, 48 h, 72 h after surgery, blood was taken to examine white blood cell count (WBC), creatinine (Cr) and blood urea nitrogen (BUN). At 72 h after surgery, morphological changes were observed by HE staining and transmission electron microscopy. Immunohistochemical staining was used to detect TNF-α, IL-10 and NF-κB expression. Blood H2S concentration was measured by deproteinization and Cystathionine-γ-lyase (CSE) activity us-ing spectrophotometric methylene blue method. Results At 24 h, 48 h, and 72 h after surgery, Levels of WBC, Cr and BUN were all elevated in Sepsis group compared with the other four groups. Levels of WBC and BUN in NaHS 8.4μmol/kg group were lower than those in NaHS 2.8μmol/kg group. At 24 h, 48 h after surgery, there is no significant difference be-tween levels of Cr in NaHS 8.4 μmol/kg group and that in NaHS 2.8 μmol/kg group , but Cr level in NaHS 8.4 μmol/kg group was marked lower than that in NaHS 2.8μmol/kg group 72 hour after surgery. Pathological features of kidney injury were also alleviated by intravenous administration of NaHS. TNF-α, NF-κB expressions in NaHS 2.8μmol/kg group and NaHS 8.4 μmol/kg group were lower than those in Sepsis group, IL- 10 expression was higher than that in Sepsis group. TNF-α, NF-κB expressions in NaHS 8.4μmol/kg group were lower than that in NaHS 2.8μmol/kg group, whereas IL-10 expression in NaHS 8.4μmol/kg group was higher than that in NaHS 2.8μmol/kg group. Compared with Control group and Sham group, H2S content and CSE expression in kidney were decreased in Sepsis group. After intravenous administration of NaHS, H2S content increased, but the CSE activity has no obvious change. Conclusion Exogenous H2S reduced kidney in-jury induced by urinary-derived sepsis through inhibiting NF-κB, decreasing TNF-αand increasing IL-10.