秋水仙碱减轻β-氨基丙腈联合血管紧张素-Ⅱ诱导的小鼠急性主动脉夹层形成OA

Objective To evaluate whether colchicine mitigates acute aortic dissection(AAD)in mice and to define its mechanistic basis.Methods Sixty 12-week-old male mice were randomized into control(n=20),model(n=20),and colchicine(Col,n=20)groups.AAD incidence,aortic diameter,and medial architecture were assessed by HE and Verhoeff-Van Gieson staining.Macrophage infiltration(CD68+cells)was quantified by flow cytometry.Systemic and local inflammatory markers(IL-6,TNF-α)were measured by ELISA,qPCR,Western blot.Smooth muscle cell(SMC)phenotypic switching and apoptosis were evaluated by α-SMA immunohistochemistry and TUNEL stai-ning,respectively.Apoptosis-related proteins(cleaved caspase-3,total caspase-3,Bax,Bcl-2)and NF-κB pathway components(phosphorylated NF-κB,total NF-κB,IκBα)were analyzed by Western blot.Results Colchicine re-duced AAD incidence from 75%to 30%(P＜0.05),limited aortic expansion,and preserved medial thickness with intact elastic lamellae.Macrophage accumulation in the aortic wall was markedly suppressed in the Col group(P＜0.05).Both serum and tissue levels of IL-6 and TNF-α were downregulated by colchicine(P＜0.05).The model group displayed increased SMC apoptosis,loss of α-SMA positivity,an elevated cleaved/total caspase-3 ratio,Bax upregulation,and Bcl-2 downregulation—changes that were attenuated by colchicine(P＜0.05).Mechanisti-cally,the Model group exhibited IκBα degradation and enhanced NF-κB phosphorylation,whereas colchicine stabi-lized IκBα and suppressed NF-κB activation(P＜0.05).Conclusions Colchicine confers protection against AAD in this murine model by interrupting NF-κB-mediated inflammatory reaction and SMC apoptosis.