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Abstract: Objective To explore the effect and mechanism of sodium butyrate (NaB) on acute kidney injury (AKI) in mice with sepsis. Methods A sepsis AKI model was prepared in 30mice and randomly divided into 3 groups: model group, NaB low-dose ( NaB-L) group, NaB high-dose (NaB-H) group, with 10 mice in each group. Another 10 mice were taken as the Sham group. HE staining was used to observe the morphological changes in the kidneys of mice. Automatic biochemical analyzer was used to detect the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The chemiluminescence method was used to determine the levels of serum kidney injury molecule-1 (KIM-1). The ELISA method was used to determine the levels of inflammatory factors such as interleukin ( IL) -1β, IL-6, and tumor necrosis factor-α ( TNF-α) in renal tissues of mice. TUNEL staining was used to observe the apoptosis in renal tissue cells of mice. Western blotting and immunohistochemical staining were used to detect the expression of proteins related to the phosphatidylinositol 3-kinase ( PI3K ) / protein kinase B ( AKT) / B cell lymphoma-2 protein(Bcl) associated X protein (Bax) pathway in renal tissues of mice in each group. Results Compared with the Sham group, the model group showed swollen, detached, and necrotic renal tubular epithelial cells, and interstitial hemorrhage accompanied by obvious inflammatory cell infiltration, and glomerular expansion or atrophy. The renal injury score, the levels of Scr, BUN and KIM-1were increased in the model group (P< 0. 05), the levels of IL-1β, IL-6 and TNF-α in renal tissues were increased ( P < 0. 05), the proportion of TUNEL-positive cells was increased ( P <0. 05), the expression of p-PI3K, p-AKT and Bcl-2 were decreased (P< 0. 05), and the expression of Bax was increased (P< 0. 05). Compared with those in the model group, the lesions of renaltubular, interstitial and glomerular in mice in the NaB-L and NaB-H groups were alleviated, the renal injury score, the levels of Scr, BUN and KIM-1 were reduced (P < 0. 05), the levels of IL-1β, IL-6 and TNF-α in renal tissues were reduced (P< 0. 05), the proportion of TUNEL-positivecells was reduced ( P < 0. 05), and the expression of p-PI3K, p-AKT and Bcl-2 were increased(P< 0. 05), and the expression of Bax was decreased (P< 0. 05). Conclusion NaB can improverenal injury in septic mice, and its mechanism may be related to the activation of PI3K / Akt signaling pathway and the inhibition of Bax expression.

Key words: sepsis, acute kidney injury, sodium butyrate