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.