Effects of inhalation of high-concentration hydrogen on acute kidney injury and mitochondrial dynamics in septic mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effects of inhalation of high-concentration hydrogen on acute kidney injury (AKI) and mitochondrial dynamics in septic mice.Methods:One hundred and twenty-eight male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=32 each) using a random number table method: sham operation group (group Sham), sham operation + hydrogen group (group Sham+ H), sepsis AKI group, and sepsis AKI+ hydrogen group (group S-AKI+ H). A mouse model of sepsis-induced AKI was developed by cecal ligation and puncture in anesthetized animals. In Sham+ H and S-AKI+ H groups, 67% H 2+ 33% O 2 was inhaled for 1 h starting from 1 and 6 h after sham operation or developing the model, respectively. Twenty mice were selected to observe the survival at 7 days after developing the model. At 24 h after developing the model, blood samples were collected for determination of serum BUN and Cr concentrations (by colorimetric analysis), and renal tissues were obtained for determination of the contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and high mobility group protein B1 (HMGB1) (by enzyme-linked immunosorbent assay), activities of superoxide dismutase (SOD) and catalase (CAT) (by spectrophotometry) and expression of dynamin-related protein 1 (Drp1) and mitofusin 2 (Mfn2) (by Western blot). The damage to the renal tubules was scored after HE staining. Results:Compared with Sham group, the survival rate was significantly decreased, the serum BUN and Cr concentrations, renal tubular damage score and contents of TNF-α, IL-1β and HMGB1 were increased, the activities of SOD and CAT were decreased, the expression of Drp1 was up-regulated, and the expression of Mfn2 was down-regulated in S-AKI group ( P<0.05), and no significant change was found in the parameters mentioned above in Sham+ H group ( P>0.05). Compared with S-AKI group, the survival rate was significantly increased, the serum BUN and Cr concentrations, renal tubular injury score and contents of TNF-α, IL-1β and HMGB1 were decreased, the activities of SOD and CAT were increased, the expression of Drp1 was down-regulated, and the expression of Mfn2 was up-regulated in S-AKI+ H group ( P<0.05). Conclusions:Inhalation of high-concentration hydrogen can alleviate AKI in septic mice, and the mechanism may be related to inhibition of renal mitochondrial fission and promotion of mitochondrial fusion.