Exploring the effect and mechanism of action of secukinumab on calcific aortic valve disease based on the IL-23/Th17 inflammatory pathway
10.3969/j.issn.1671-7856.2024.08.009
- VernacularTitle:基于IL-23/Th17炎症通路探讨司库奇尤单抗对钙化性主动脉瓣膜病的影响及作用机制
- Author:
Xinxin LI
1
;
Ning ZHANG
;
Guangling FENG
;
Zhenzhen LAN
;
Jiao GUO
;
Xincan LIU
Author Information
1. 宁德师范学院附属宁德市医院 消化内科,福建 宁德 352000
- Keywords:
IL-23/Th17;
calcific aortic valve disease;
inflammation;
secukinumab
- From:
Chinese Journal of Comparative Medicine
2024;34(8):78-86
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe whether the IL-23/Th17 inflammatory pathway is involved in the development of calcific aortic valve disease,and whether secukinumab can delay the progression of calcific aortic valve disease by inhibiting this pathway.Methods Forty-seven mice were divided into a blank control group,model group,and secukinumab group according to the random number table method.The blank control group was fed normal chow,while the model group and secukinumab group were fed pro-calcification chow for 16 weeks to establish a calcific aortic valve disease model.After intervention with secukinumab for 4 weeks,peak flow velocity changes in the aortic valves were detected under Doppler ultrasonography in all mice.Relevant indexes were determined by hematoxylin and eosin staining,Von Kossa staining,immunohistochemical staining,ELISA,and qPCR.Results Compared with the model group,the secukinumab group showed significantly reduced peak flow velocity(P＜0.05)and serum IL-6,IL-17,and IL-23 levels(P＜0.05)in the aortic valve.Compared with the secukinumab group,the model group's leaflet thickness was significantly increased,and there were more calcium deposits.Immunohistochemical result showed that macrophage infiltration(P＜0.05),IL-17A(P＜0.05)and IL-23(P＞0.05)levels in the valve leaflets were reduced in the secukinumab group compared with the model group.PCR result suggested that the expression of STAT3,BMP-2,and α-SMA mRNA was significantly lower in the secukinumab group than the model group(P＜0.05).Conclusions The IL-23/Th17 inflammatory pathway is involved in the pathogenesis of calcific aortic valve disease.The inflammation,fibrosis,osteogenic differentiation,and calcification of mouse valves were alleviated after intervention with secukinumab,which may delay disease progression by inhibiting the IL-23/Th17 inflammatory pathway.
