Sinomenine ameliorates vascular calcification by inhibiting pyroptosis-related molecules and AEG-1 in chronic kidney disease

作者：Tang Z, Yu F, Peng Z, Gao N, Liao Z, Zhao S, Xia Y, Fu H, Zhong S, Long W, He Z · 发表于：European journal of pharmacology · 年份：2025 · DOI：10.1016/j.ejphar.2025.177594 · 研究领域：Morphinans、Vascular Calcification、Renal Insufficiency, Chronic、Pyroptosis、Cell Adhesion Molecules、Animals、Rats, Sprague-Dawley、Rats、Male、Membrane Proteins、NLR Family, Pyrin Domain-Containing 3 Protein、Aorta

BACKGROUNDS: Vascular calcification (VC) is an important factor for mortality in chronic kidney disease (CKD). Sinomenine can suppress atherosclerosis. However, its role in CKD-associated-vascular calcification and mechanisms remain unclear. METHODS: Sprague-Dawley rats that were fed with high-phosphorus diet and adenine suspension were used to construct the calcification model in CKD. Calcification from rats or cells were analyzed using micro-CT and alizarin red staining. Levels of NLRP-3, Caspase-1, GSDMD and AEG-1 were measured by qPCR, western blotting, and immunohistochemistry. Transfection experiment was used in function study. RESULTS: CKD rats fed with high-phosphorus diet and adenine suspension increased aortic calcification over time. Micro-CT images revealed the distribution and severity of the calcification, and these lesions were significantly decreased in the Sinomenine (SIN) group. This is similar to the results obtained for the AR staining of translucent samples. Additionally, aortas from CKD rats that were treated with 30 mg/kg/d SIN showed a down-regulation of NLRP3, Caspase-1, GSDMD and AEG-1 expression compared with aortas from CKD rats. Sinomenine exhibited similar inhibitory effects on NLRP3 and Caspase-1 as VX-765 in the aortas of uremic rats and calcified VSMCs. Moreover, VSMC transfected with pc-AEG-1 accelerated the VSMC calcification while transfection with si-AEG-1 ameliorated the calcification. Importantly, sinomenine abolished the VSMC calcific...