摘要
目的探讨乔松素对糖尿病心肌病(DCM)大鼠心肌炎症及干扰素基因刺激因子/TANK结合激酶1/干扰素调节因子3(STING/TBK1/IRF3)信号通路的影响。方法构建糖尿病心肌病大鼠模型,将造模成功大鼠分为模型组,乔松素低、高剂量组及乔松素高剂量+STING通路激活剂DMXAA组(乔松素高剂量+DMXAA组),每组各12只,另取12只正常大鼠作为对照组;检测大鼠心功能及糖代谢水平;ELISA法检测炎性相关因子水平及心肌损伤相关指标水平;HE染色观察心肌组织病理变化;Masson染色观察心肌组织纤维化程度;免疫组化法检测心肌组织纤维化相关蛋白赖氨酰氧化酶(LOX)表达;Western Blot法检测STING/TBK1/IRF3信号通路相关蛋白表达。结果模型组较对照组心肌组织结构与细胞排列紊乱,心肌纤维断裂且间隙变宽,心肌细胞肥大,有明显炎性细胞浸润,蓝色胶原纤维增多,心肌胶原纤维化占比升高,LVEF、LVFS、Em/Am降低,FBG、FINS、CK-Mb、cTnI、TNF-α、IL-6、IL-1β水平及LOX、p-STING/STING、p-TBK1/TBK1、p-IRF3/IRF3表达升高(P<0.05);乔松素低、高剂量组较模型组心肌组织结构与细胞排列相对工整,心肌纤维断裂及间隙增宽减少,心肌细胞形态趋于正常,炎性细胞浸润不明显,蓝色胶原纤维减少,心肌胶原纤维化占比降低,LVEF、LVFS、Em/Am升高,FBG、FINS、CK-Mb、cTnI、TNF-α、IL-6、IL-1β水平及LOX、p-STING/STING、p-TBK1/TBK1、p-IRF3/IRF3表达降低(P<0.05);乔松素高剂量+DMXAA组较乔松素高剂量组心肌组织损伤严重,其纤维化及炎性细胞浸润程度加剧,蓝色胶原纤维增多,心肌胶原纤维化占比升高,LVEF、LVFS、Em/Am降低,FBG、FINS、CK-Mb、cTnI、TNF-α、IL-6、IL-1β水平及LOX、p-STING/STING、p-TBK1/TBK1、p-IRF3/IRF3表达升高(P<0.05)。结论PIN可改善DCM大鼠心肌炎症,其作用机制与抑制STING/TBK1/IRF3信号通路有关。
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 inflammationrelated 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-1βand 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-1βand 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-1βand 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.
作者
张来军
郑乃汭
胡仕坤
何敏
刘玮芳
马丽
王婧
彭青
申岩
ZHANG Laijun;ZHENG Nairui;HU Shikun;HE Min;LIU Weifang;MA Li;WANG Jing;PENG Qing;SHEN Yan(Department of Nursing,Henan Vocational College of Nursing,Anyang 455000 Henan,China;Department of Endocrinology,Anyang People's Hospital,Anyang 455000 Henan,China)
出处
《中药新药与临床药理》
北大核心
2025年第2期175-181,共7页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
河南省教育厅教育科学规划2024年度一般课题立项(2024YB0517)。
