探讨隐丹参酮(cryptotanshinone,CTS)是否通过树突状细胞相关C型凝集素1(Dectin-1)信号通路调节巨噬细胞极化发挥抗心肌缺血的作用.选用6周龄雄性C57BL/6小鼠制作心肌缺血模型,分为假手术组、模型组、CTS低剂量组(21 mg-kg-1·d-1)、CTS高剂量组(84 mg-kg-1·d-1)、达格列嗪组(0.14 mg-kg-1·d-1).分别检测各组心功能和血清酶水平、Dectin-1表达以及心肌梗死区巨噬细胞极化和中性粒细胞浸润程度.进一步利用脂多糖(lipopolysaccharide,LPS)/干扰素(interferon,IFN)-γ刺激RAW264.7构建M1型巨噬细胞体外模型,观察CTS对巨噬细胞极化状态的影响,并检测Dectin-1信号通路下游关键蛋白的变化.CTS组相比模型组小鼠,心功能和心肌损伤程度均明显改善,心肌梗死区M2/M1型巨噬细胞比例显著升高,中性粒细胞浸润明显减少,同时Dectin-1呈现低表达.体外实验显示,CTS可下调M1型并升高M2型标志基因的表达,并降低Dectin-1的含量及其通路相关蛋白脾酪氨酸激酶(spleen tyrosine kinase,Syk)、蛋白激酶B(protein kinase B,Akt)、核因子-κB p65(nuclear factor-kappaB p65,NF-κB p65)和细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)1/2 的磷酸化,促进信号传导及转录激活蛋白(signal transducer and activator of transcription,STAT)6的磷酸化.结果表明隐丹参酮通过Dectin-1信号通路调节巨噬细胞极化发挥抗心肌缺血损伤作用.
Anti-myocardial ischemic injury effects and mechanisms of cryptotanshinone in regulating macrophage polarisation through Dectin-1 signalling pathway
The aim of this study was to investigate the potential mechanism by which cryptotanshinone(CTS)may exert its anti-myo-cardial ischemic effect through the regulation of macrophage polarization via the dendritic cell-associated C-type lectin 1(Dectin-1)signaling pathway.Male C57BI/6 mice,aged six weeks,were utilized to establish myocardial ischemia models and were subsequently divided into five groups:sham,model,CTS low-dose(21 mg·kg-1·d-1),CTS high-dose(84 mg·kg-1·d-1),and dapagliflozin(0.14 mg·kg-1·d-1).The cardiac function,serum enzyme levels,Dectin-1 expression,macrophage polarization,and neutrophil infil-tration in the myocardial infarction area were assessed in each group.An in vitro model of M1-type macrophages was constructed using lipopolysaccharide/interfe-ron-γ(LPS/IFN-γ)stimulated RAW264.7 cells to investigate the impact of CTS on macrophage polarization and to examine alterations in key proteins within the Dectin-1 signaling pathway.In the CTS group,compared to the model group mice,there was a significant improvement in the cardiac function and myocardial injury,along with a notable increase in the ratio of M2/M1-type macrophages in the myocardial infarcted area and a decrease in neutrophil infiltration.Additionally,Dectin-1 exhibited low ex-pression.The results of in vitro experiments demonstrated that CTS can decrease the expression of M1-type marker genes and increase the expression of M2-type marker genes.Besides,it can decrease the levels of Dectin-1 and the phosphorylation of its associated pro-teins,including spleen tyrosine kinase(Syk),protein kinase B(Akt),nuclear factor-kappaB p65(NF-κB p65),and extracellular signal-regulated protein kinases(ERK1/2).Additionally,CTS was found to enhance the phosphorylation of signal transducer and acti-vator of transcription-6(STAT6).The above results suggest that CTS exerts its anti-myocardial ischemic injury effect by regulating macrophage polarization through the Dectin-1 signaling pathway.
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