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  

Exploring the effect and mechanism of action of secukinumab on calcific aortic valve disease based on the IL-23/Th17 inflammatory pathway

作　　者：李欣欣 张宁[2] 冯光玲 兰真真 郭娇[2] 刘新灿[2] LI Xinxin;ZHANG Ning;FENG Guangling;LAN Zhenzhen;GUO Jiao;LIU Xincan(Department of Gastroenterology,Ningde Municipal Hospital of Ningde Normal University,Ningde 352000,China;Heart Center,the First Affiliated Hospital of Henan University of CM,Zhengzhou 450000)

机构地区：[1]宁德师范学院附属宁德市医院消化内科,福建宁德352000 [2]河南中医药大学第一附属医院心脏中心,郑州450000

出　　处：《中国比较医学杂志》2024年第8期78-86,共9页Chinese Journal of Comparative Medicine

摘　　要：目的观察IL-23/Th17炎症通路是否参与钙化性主动脉瓣膜病的发生发展,司库奇尤单抗是否可以通过抑制IL-23/Th17炎症通路延缓钙化性主动脉瓣膜病的进展。方法按随机数字表法将47只小鼠分为空白对照组、模型组和司库奇尤单抗组。空白对照组给予正常饲料喂养,模型组、司库奇尤单抗组给予促钙化饲料喂养16周后建立钙化性主动脉瓣膜病模型,司库奇尤单抗对司库奇尤单抗组小鼠干预4周后,在多普勒超声下检测所有小鼠主动脉瓣峰值流速变化;采用HE染色、Von Kossa染色、免疫组化染色、ELISA和实时荧光定量PCR进行相关指标测定。结果与模型组相比,司库奇尤单抗组药物干预4周后,能够显著降低主动脉瓣膜的峰值流速(P<0.05),降低血清IL-6、IL-17、IL-23水平(P<0.05);与司库奇尤单抗组相比,模型组瓣叶厚度明显增加且有更多的钙盐沉积;免疫组化结果显示司库奇尤单抗组与模型组相比,瓣叶中巨噬细胞(P<0.05)、IL-17A(P<0.05)、IL-23(P>0.05)浸润均减少。PCR结果提示,与模型组相比,司库奇尤单抗组的STAT3、BMP-2及α-SMA mRNA的表达均显著减少(P<0.05)。结论IL-23/Th17炎症通路参与了钙化性主动脉瓣膜病的发病过程,经司库奇尤单抗干预后小鼠瓣膜的炎症、纤维化、成骨分化及钙化情况均有所缓解,司库奇尤单抗可能通过抑制IL-23/Th17炎症通路而延缓疾病进展。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,andα-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.

关 键 词：IL-23/Th17 钙化性主动脉瓣膜病 炎症 司库奇尤单抗 

分 类 号：R-33[医药卫生]