Study on the Molecular Mechanism of Angiotensin Promoting the Process of Intrauterine Adhesions by Regulating the NLRP3 Inflammasome Pathway.

OBJECTIVE

The pathogenesis of intrauterine adhesions remains unclear, with angiotensin potentially contributing to their progression.

METHODS

A rat model of intrauterine adhesion (IUA) was constructed. Histomorphological analysis of endometrial architecture was performed using hematoxylin-eosin (HE) staining. Protein expression profiles of NLRP3, IL-1β, α-smooth muscle actin (α-SMA), and E-cadherin were quantified through Western blot analysis. PCR detection was performed using primer sequences specific to the factors of interest.

RESULTS

The rat IUA model exhibited characteristic uterine wall adhesions, marked inflammatory infiltration, and significantly reduced vimentin expression compared to sham-operated controls. Systemic analyses revealed Ang II's concentration-dependent promotion of IUA progression, with 10-5-10-7 mol/L doses significantly elevating endometrial epithelial cell (EEC) proliferation (p<0.05), collagen I/III secretion (p<0.05), and EMT marker dysregulation. Mechanistically, Ang II activated the NLRP3 inflammasome pathway, driving IL-1β overexpression and pyroptosis, with maximal adhesion severity at 10-5 mol/L. NLRP3 agonism exacerbated inflammatory responses, while siRNA-mediated NLRP3 knockdown restored E-cadherin expression and attenuated N-cadherin, effectively reversing EMT progression.

CONCLUSION

This study demonstrates that angiotensin II drives intrauterine adhesion progression through NLRP3 inflammasome-mediated inflammatory escalation and fibrotic remodeling. The identified Ang II-NLRP3 axis may offer a dual therapeutic target for mitigating both pathological inflammation and endometrial fibrosis in adhesion prevention.