Irisin protects female mice with LPS-induced endometritis through the AMPK/NF-κB pathway

Objective(s): This research was designed to determine the role of irisin in lipopolysaccharide (LPS)-induced endometritis in female mice. Materials and Methods: Animals were randomly assigned into sham, sham + irisin, LPS, LPS + irisin (۰.۱, ۱, ۱۰ μg/kg), and LPS + irisin + compound C groups. Histological features and expression of AMPK, NF-κB, inflammatory mediators, and oxidative stress markers were compared among different groups. Results: The results showed that LPS resulted in obvious uterus damage, meanwhile, the inflammatory mediators (COX-۲, iNOS, IL-۱β, IL-۶, and TNF-α), as well as NF-κB in the uterine tissue, were significantly increased and the level of adenosine monophosphate-activated protein kinase (AMPK) was reduced. Nevertheless, pretreatment with irisin reversed the phenomena caused by LPS. Interestingly, compound C (AMPK inhibitor) abolished irisin’s effects on the uterus, which suggested that irisin’s beneficial function was achieved through regulating the AMPK-NF-κB pathway. Moreover, LPS-induced alterations of oxidative factors (MnSOD, GSH, and MDA) were reversed significantly by pretreatment with irisin. This data indicated irisin’s beneficial function was also related to antioxidation besides anti-inflammation.  Conclusion: Our study implies that irisin is a potential therapeutic agent for endometritis.

Keywords:

AMP-activated protein kinases , Endometritis , Inflammation , Irisin , Lipopolysaccharide NF-κB