Background
We aimed to study the effects and the underlying mechanisms of Diosmetin (DIOS) in rats with sepsis-induced acute kidney injury (AKI).
Conclusion
DIOS may reduce sepsis-induced AKI through enhancing the TUG1/Nrf2/HO-1 pathway.
Methods
The AKI model in RMCs was induced using LPS, and the cells were then treated with DIOS. Cell viability, apoptosis, inflammatory response, and antioxidant were measured using MTT, Flow cytometry, ELISA, and Lucigenin assay, respectively. The correlation between TUG1 and Nrf2 was confirmed by RNA pull-down and RNA immunoprecipitation. Real-time quantitative PCR and Western blot were performed to detect the expressions of gene and proteins during the development of AKI. The effects of lncRNA-TUG1 silencing and Nrf2 silencing on cell physiological functions were detected. Moreover, a rat sepsis-induced AKI model followed by Hematoxylin & Eosin (H&E) and immunofluorescence staining were performed.
Results
The experimental concentration of DIOS was determined to be 20 μM. After LPS treatment, the activity of RMCs was decreased, the apoptosis rate, inflammation and oxidative stress damage were increased, moreover, the expression of Nrf2/HO-1 signal axis was inhibited and caspase-3 was activated. However, DIOS significantly reversed these effects caused by LPS treatment, and increased the expression of lncRNA-TUG1, but lncRNA-TUG1 silencing effectively reversed the effects of DIOS. In addition, lncRNA-TUG1 was found to interact with Nrf2. Overexpression of TUG1 could reduce the damage of LPS caused to cell physiological functions, which were reversed by siNrf2. Thus, DIOS treatment could improve the physiological and pathological damages of renal tissues in AKI rats.