To investigate the protective effect of PPARα agonist WY14643 on stress-induced liver injury.

Fourteen female SD rats were randomly divided into control group (NC) and model group (SLI), 7 in each group. The stress-induced liver injury model was established by the water immersion restraint method. After 21 days of modeling, the morphological changes of liver tissue were observed by HE staining method, serum corticosterone (CORT), alanine transaminase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), total cholesterol (TC), triglyceride (TG) contents were measured by ELISA method, transcriptome sequencing technology was used to find the differentially expressed genes between control group and model group, and qRT-PCR was used to verify the differentially expressed genes. The differentially expressed gene PPARα agonist WY14643 was selected, and 24 SD rats were randomly divided into control group, SLI, WY14643 low-dose group (WYL) and WY14643 high-dose group (WYH). One hour before the daily restraint stress, WYL and WYH groups were intraperitoneally injected with 0.5 and 1 mg·kg^-1 of WY14643, respectively. The control group and model group were intraperitoneally injected with the equal doses of saline, and water immersion restraint stress experiment was performed to observe whether WY14643 has anti-stress protective effect and molecular mechanism of liver injury.

ELISA results showed that WY14643 could reduce rat serum CORT, ALT, AST, TNF-α, IL-1β, TC, TG contents. The results of liver HE staining showed that WY14643 could reduce liver damage caused by stress. Western blot results showed that WY14643 could reduce the protein expression of PI3K, AKT and NF-κB in rat liver.

WY14643 can improve the liver damage caused by water immersion restraint stress, and this effect may be related to its inhibition of PI3K/AKT/NF-κB pathway.