中药新药与临床药理2025，Vol.36Issue(2)：175-181,7.DOI:10.19378/j.issn.1003-9783.2025.02.003
乔松素调节STING/TBK1/IRF3信号通路对糖尿病心肌病大鼠心肌炎症的影响
Effects of Pinocembrin on Myocardial Inflammation in Diabetic Cardiomyopathy Rats by Modulating the STING/TBK1/IRF3 Signaling Pathway
摘要
Abstract
Objective To investigate the effects of pinocembrin(PIN)on myocardial inflammation and stimulator of interferon gene/TANK-binding kinase 1/interferon regulatory factor 3(STING/TBK1/IRF3)signaling pathway in diabetic cardiomyopathy(DCM)rats.Methods A DCM rat model was constructed,and the modeled rats were separated into a model group,PIN low-and high-dose groups,and a PIN high-dose+STING pathway activator DMXAA group(high-dose of PIN+DMXAA group),with 12 rats in each group.Twelve normal rats were taken as a control group.Cardiac function and glucose metabolism levels were detected.ELISA was used to detect the level of inflammation-related factors and the level of myocardial injury-related indexes.HE staining was used to observe the pathological changes of myocardial tissue.Masson staining was used to observe the degree of myocardial tissue fibrosis.The expression of fibrosis-related protein lysyl oxidase(LOX)in myocardial tissue was detected by immunohistochemistry.Western Blot was used to detect the expression of proteins related to STING/TBK1/IRF3 signaling pathway.Results Myocardial tissue structure and cellular arrangement were disordered in the DCM group compared with the control group,myocardial fibers were broken and the gap was widened,cardiomyocytes were hypertrophied with obvious inflammatory cell infiltration,blue collagen fibers were increased,and the percentage of myocardial collagenous fibrosis was elevated.The LVEF,LVFS,Em/Am values decreased.The levels of FBG,FINS,CK-Mb,cTnI,TNF-α,IL-6,IL-1β and the expression of LOX,p-STING/STING,p-TBK1/TBK1 and p-IRF3/IRF3 elevated(P<0.05).Myocardial tissue structure and cell arrangement were relatively neat in PIN low-and high-dose groups compared with the DCM group,the breakage of myocardial fibers and the amplification of interstitial space were reduced,the morphology of myocardial cells tended to be normal,the infiltration of inflammatory cells was insignificant,and the blue collagen fibers were reduced,the percentage of myocardial collagen fibrosis decreased.The LVEF,LVFS,Em/Am values increased,the levels of FBG,FINS,CK-Mb,cTnI,TNF-α,IL-6,IL-1β and the expression of LOX,p-STING/STING,p-TBK1/TBK1,p-IRF3/IRF3 decreased(P<0.05).Myocardial tissue damage was more severe in the high-dose of PIN+DMXAA group than in PIN high-dose group,with increased fibrosis,inflammatory cell infiltration and blue collagen fibers.The percentage of myocardial collagen fibrosis elevated.The LVEF,LVFS,Em/Am values decreased.The levels of FBG,FINS,CK-Mb,cTnI,TNF-α,IL-6,IL-1β and the expression of LOX,p-STING/STING,p-TBK1/TBK1,p-IRF3/IRF3 elevated(P<0.05).Conclusion Pinocembrin ameliorates myocardial inflammation in diabetic cardiomyopathy rats.Its mechanism of action is related to the inhibition of STING/TBK1/IRF3 signaling pathway.关键词
乔松素/干扰素基因刺激因子/TANK结合激酶1/干扰素调节因子3信号通路/糖尿病心肌病/心肌炎症/大鼠Key words
Pinocembrin/stimulator of interferon gene/TANK-binding kinase 1/interferon regulatory factor 3 signaling pathway/diabetic cardiomyopathy/myocardial inflammation/rats分类
医药卫生引用本文复制引用
张来军,郑乃汭,胡仕坤,何敏,刘玮芳,马丽,王婧,彭青,申岩..乔松素调节STING/TBK1/IRF3信号通路对糖尿病心肌病大鼠心肌炎症的影响[J].中药新药与临床药理,2025,36(2):175-181,7.基金项目
河南省教育厅教育科学规划2024年度一般课题立项(2024YB0517). （2024YB0517）
