Abstract:

Objective To investigate the inhibitory effect of rosiglitazone on ferroptosis of renal tubular epithelial cells in the mice with acute kidney injury （AKI） induced by lipopolysaccharide （LPS）， and to clarify its mechanism. Methods A total of 18 C57BL/6 male mice were randomly divided into control group（n=6）， LPS group（n=6），and LPS +rosiglitazone group （n=6）. The mice in LPS group and LPS+rosiglitazone group were injected with 10 mg·kg^－1 LPS intraperitoneally； the mice in LPS+rosiglitazone group were injected with 0.5 mg·kg^－1 rosiglitazone via the tail vein 30 min before LPS injection；the mice in control group were injected with the same volume of normal saline. The mice were sacrificed 24 h after LPS injection， and the kidney tissue and serum were collected. HE staining was used to observe the pathomorphology of kidney tissue of the mice in various groups； the levels of serum creatinine （CRE） and urea nitrogen （BUN） of the mice were detected by spectrophotometry； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of acyl CoA synthetase long-chain family member 4（ACSL4），glutathione peroxidase 4（GPX4）， solute carrier family 7 member 11（SLC7A11），interleukin-6（IL-6）， interleukin-1β（IL-1β）， and tumor necrosis factor-α（TNF-α） mRNA in kidney tissue of the mice in various groups；Western blotting method was used to detect the expression levels of ACSL4，GPX4， and SLC7A11 proteins in kidney tissue of the mice in various groups. Results The HE staining results showed that compared with control group， there were vacuoles in the renal tubule lumen of the mice in LPS group， the score of renal tubular injury was increased significantly（P<0.01）； compared with LPS group，the renal tubular epithelial cells in kidney tissue of the mice in LPS+rosiglitazone group were closely arranged， there was almost no protein tube， and the score of renal tubular injury of the mice was decreased significantly（P<0.01）.Compared with control group，the levels of CRE and BUN in serum of the mice in LPS group were increased（P<0.01）； compared with LPS group， the levels of CRE and BUN in serum of the mice in LPS+rosiglitazone group were decreased significantly（P<0.01）.The RT-qPCR and Western blotting results showed that compared with control group，the expression levels of ACSL4 mRNA and protein in kidney tissue of the mice in LPS group were increased（P<0.01），the expression levels of GPX4 and SLC7A11 mRNA and proteins were decreased（P<0.01），and the expression levels of IL-6， IL-1β， and TNF-α mRNA were increased（P<0.01）； compared with LPS group， the expression levels of ACSL4 mRNA and protein in kidney tissue of the mice in LPS+rosiglitazone group were decreased（P<0.01），the expression levels of GPX4 and SLC7A11 mRNA and proteins were increased（P<0.01），and the expression levels of IL-6， IL-1β，and TNF-α mRNA were decreased（P<0.01）. Conclusion Rosiglitazone can ameliorate the ferroptosis of renal tubular epithelial cells in the AKI mice induced by LPS through regulating ACSL4.

Key words: Acute kidney injury, Acyl CoA synthetase long-chain family member 4, Ferroptosis, Rosiglitazone