丹参酮ⅡA调控微小RNA-155-5p/细胞因子信号抑制因子1/核因子-κB轴减轻小鼠动脉粥样硬化斑块炎症OA
Tanshinone ⅡA regulates the miR-155-5p/SOCS1/NF-κB axis to alleviate inflammation of atherosclerotic plaques in mice
目的:探究丹参酮ⅡA对小鼠动脉粥样硬化斑块炎症的影响及机制.方法:将50只雄性载脂蛋白E基因敲除(ApoE-/-)小鼠随机分为对照组、模型组、丹参酮ⅡA组、丹参酮Ⅱ A+激动剂阴性对照(Agomir NC)组、丹参酮Ⅱ A+miR-155-5p Agomir组,每组10只.高脂饲料饲养雄性ApoE-/-小鼠12周构建动脉粥样硬化模型.实时荧光定量聚合酶链式反应(RT-qPCR)检测主动脉组织miR-155-5p表达,酶联免疫吸附试验(ELISA)试剂盒检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、IL-1β、IL-10水平,苏木精-伊红(HE)、油红O染色检测主动脉组织病理损伤及脂质沉积情况,蛋白质印迹(Western blot)检测主动脉组织白细胞分化抗原86(CD86)、诱导型一氧化氮合酶(iNOS)、CD206、精氨酸酶1(Arg1)、细胞因子信号抑制因子1(SOCS1)蛋白表达及磷酸化核因子-κB p65(p-NF-κB p65)/NF-κB p65比值.结果:相对于对照组,模型组小鼠miR-155-5p、TC、TG、LDL-C、主动脉脂质沉积面积占比、CD86、iNOS、IL-6、TNF-α、IL-1β、p-NF-κB p65/NF-κB p65 比值升高(均 P＜0.05),HDL-C、CD206、Arg1、IL-10、SOCS1 降低(均P＜0.05),主动脉中可见明显的动脉斑块;相对于模型组,丹参酮Ⅱ A组上述指标结果有明显改善(均P＜0.05);miR-155-5p Agomir部分逆转了丹参酮Ⅱ A对动脉粥样硬化小鼠斑块炎症的改善作用(P＜0.05).结论:丹参酮ⅡA可能通过下调M1型、上调M2型极化相关蛋白表达减轻动脉粥样硬化小鼠的斑块炎症,其机制可能与调控miR-155-5p/SOCS1/NF-κB 轴有关.
Objective:Exploring the effects and mechanism of tanshinone Ⅱ A on inflammation in mouse athero-sclerotic plaques.Methods:Fifty male apolipoprotein E-/-(ApoE-/-)mice were randomly divided into control group,model group,tanshinone ⅡA group,tanshinone ⅡA+agomir negative control(Agomir NC)group,and tan-shinone Ⅱ A+miR-155-5p Agomir group,with 10 mice in each group.Male ApoE-/-mice were fed on high-fat diet for 12 weeks to construct an atherosclerotic mouse model.Real-time fluorescent quantitative polymerase chain reac-tion(RT-qPCR)was used to detect the expression of miR-155-5p in aortic tissue.Enzyme-linked immunosorbent as-say(ELISA)kits were used to detect the levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),interleukin 6(IL-6),tumor necrosis factor α (TNF-α),IL-1β,and IL-10 in serum.Hematoxylin-eosin(HE)staining and oil red O staining were used to detect the pathological damage and lipid deposition of aortic tissue.Western blot was used to detect the expression of cluster of differentiation 86(CD86),inducible nitric oxide synthase(iNOS),CD206,arginase 1(Arg1)and suppressor of cyto-kine signaling 1(SOCS1)proteins and the phosphorylated nuclear factor-κB p65(p-NF-κB p65)/NF-κB p65 ratio in aortic tissue.Results:Compared with the control group,the miR-155-5p,TC,TG,LDL-C,aortic lipid deposition area,CD86,iNOS,IL-6,TNF-α,IL-1β,and p-NF-κB p65/NF-κB p65 ratio increased in the model group(P＜0.05),and HDL-C,CD206,Arg1,IL-10,SOCS1 decreased(all P＜0.05),and obvious atherosclerotic plaques were observed in the aorta.Compared with the model group,the above indicators in the Tanshinone ⅡA group showed significant im-provement(all P＜0.05).miR-155-5p Agomir partially reversed the improvement effect of Tanshinone ⅡA on plaque inflammation in atherosclerotic mice(P＜0.05).Conclusion:Tanshinone ⅡA might help reduce plaque in-flammation in atherosclerotic mice by downregulating M1-type and upregulating M2-type polarization-related protein expression,and its mechanism could be related to regulating the miR-155-5p/SOCS1/NF-κB axis.
沈忱;马晓佳;关丽娜;何婷婷
呼伦贝尔市人民医院心血管内科,内蒙古呼伦贝尔 021000呼伦贝尔市人民医院心血管内科,内蒙古呼伦贝尔 021000呼伦贝尔市人民医院心血管内科,内蒙古呼伦贝尔 021000呼伦贝尔市人民医院心血管内科,内蒙古呼伦贝尔 021000
医药卫生
丹参酮ⅡA动脉粥样硬化微小核糖核酸-155-5p细胞因子信号抑制因子1核因子-κB巨噬细胞极化
Tanshinone ⅡAAtherosclerosisMir-155-5pSOCS1NF-κBMacrophage polarization
《陕西医学杂志》 2026 (9)
1202-1207,6
内蒙古自治区自然科学基金面上(联合)资助项目[2024MS(LH)0121]
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