Abstract
Background:
Acute kidney injury (AKI) is closely linked to the pathogensis of sepsis. Oxidative stress can affect the development of AKI by increasing damage to renal tubular epithelial cells. Astragaloside IV (AS-IV), a natural saponin that is widly verifed beneficial for ameliorating sepsis-induced kidney injury. However, the underlying mechanisms of AS-IV on relieving oxidative stress in renal tubular epithelial cells are yet to be established.
Purpose:
We aimed to investigate whether AS-IV could attenuate mitochondrial dysfunction and apoptosis in renal tubular epithelial cells and reveal its underlying mechanisms.
Methods:
For the in vivo study, mice were divided into four groups(n=6): sham+saline, CLP+saline, CLP+AS-IV-low dosage(5 mg/kg), CLP+AS-IV-high dosage(10 mg/kg), After 6 h or 24 h of treatment, the renal injuries were assessed based related parameters of blood, protein and histopathological examination. Immunohistochemistry and ELISA were used to examine renal function. The molecular mechanism of AS-IV inhibited apoptosis and mitochondrial damage were monitored by flow cytometry and western blot analysis in HK-2 cells.
Results:
We found that AS-Ⅳ ameliorates renal vacuolization, brush border loss, mitochondrial ultrastructure changes in sepsis-induced AKI, and the apoptosis and oxidative damage were greatly mitigated by AS-Ⅳ(10 mg/kg)-treated group. Abnormal changes in mitochondrial morphology and mitochondrial membrane potential were alleviated, and the expression of mitochondrial complex protein Ⅰ (NDUFB8) and mitochondrial complex protein Ⅱ (SDHB8) increased with (10 mg/kg)-treated group. Tubular epithelial cell apoptosis in AS-Ⅳ(20 μM)-treated cells was reduced by the Bax and cleaved caspase3 pathway.
Conclusion:
These study demonstrated that AS-IV protects against sepsis-induced kidney tubular injury by alleviating oxidative stress, mitochondrial dysfunction possibly associated with the restored cleaved caspase3 pathway.
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