Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low...Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low-dose curcumin(50 mg/kg),high-dose curcumin(200 mg/kg),high-dose curcumin plus a scrambled control antagomir,or high-dose curcumin plus anti-miR-29b treatments.Cardiac function was assessed by echocardiography.Fibrosis was evaluated by histology,collagen volume fraction,and hydroxyproline content.Expression of miR-29b,HDAC4,and fibrosis-related markers(Col1a1,Col3a1,TGF-β1)was measured by quantitative RT-PCR and Western blotting assays.Myocardial procollagen type I carboxy-terminal propeptide was determined by ELISA,and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit.Results:Curcumin improved cardiac function,reduced fibrosis,restored miR-29b expression,and suppressed HDAC4 expression and activity in a dose-dependent manner.Furthermore,curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels,confirming reduced collagen synthesis.Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin.Conclusions:Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.展开更多
目的探讨γ干扰素(interferon-gamma,INF-γ)、微小RNA-29a(microRNA-29a,miR-29a)、原癌基因PIM-1(proto-oncogene PIM-1,PIM-1)标志物在结核性胸膜炎合并胸腔积液中的表达水平变化及其与临床特征的关系。方法选取2021年5月—2023年6...目的探讨γ干扰素(interferon-gamma,INF-γ)、微小RNA-29a(microRNA-29a,miR-29a)、原癌基因PIM-1(proto-oncogene PIM-1,PIM-1)标志物在结核性胸膜炎合并胸腔积液中的表达水平变化及其与临床特征的关系。方法选取2021年5月—2023年6月在某医院就诊的107例结核性胸膜炎患者为研究对象,按照诊断结果分为结核性胸膜炎合并胸腔积液组(n=69)和单纯结核性胸膜炎组(n=38)。对比两组INF-γ、miR-29a、PIM-1表达水平差异,Spearman相关系数分析INF-γ、miR-29a、PIM-1表达水平与结核性胸膜炎合并胸腔积液的相关性;受试者操作特征(receiver operator characteristic,ROC)曲线分析INF-γ、miR-29a、PIM-1及其联合检测对结核性胸膜炎合并胸腔积液的预测效能,计量资料数据比较分析采用t检验,计数资料的比较采用χ^(2)检验。结果与单纯结核性胸膜炎组相比,结核性胸膜炎合并积液组的INF-γ(t=-5.440,P<0.001)、miR-29a(t=-3.561,P=0.001)、PIM-1(t=-3.232,P=0.002)均升高;Spearman相关系数分析显示,INF-γ、miR-29a、PIM-1表达水平与结核性胸膜炎合并胸腔积液呈正相关(r=0.443,P<0.001;r=0.332,P<0.001;r=0.291,P=0.002);ROC曲线显示,INF-γ、miR-29a、PIM-1单独及联合检测预测结核性胸膜炎合并胸腔积液的曲线下面积(area under the curve,AUC)分别为0.764、0.701、0.663和0.838,与INF-γ、miR-29a、PIM-1单独检测相比,联合检测对结核性胸膜炎合并胸腔积液具有较高的诊断效能(Z=1.983、2.168、2.859,P=0.047、0.030、0.004)。结论结核性胸膜炎合并胸腔积液患者INF-γ、miR-29a、PIM-1表达水平均表现为特异性的上调,这种联合检测对预测结核性胸膜炎患者是否合并胸腔积液具有良好的预测效能,值得临床推广应用。展开更多
基金supported by China International Medical Foundation(Z-2019-42-1908-4)Natural Science Basic Research Program of Shaanxi Province(2019JM-440).
文摘Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low-dose curcumin(50 mg/kg),high-dose curcumin(200 mg/kg),high-dose curcumin plus a scrambled control antagomir,or high-dose curcumin plus anti-miR-29b treatments.Cardiac function was assessed by echocardiography.Fibrosis was evaluated by histology,collagen volume fraction,and hydroxyproline content.Expression of miR-29b,HDAC4,and fibrosis-related markers(Col1a1,Col3a1,TGF-β1)was measured by quantitative RT-PCR and Western blotting assays.Myocardial procollagen type I carboxy-terminal propeptide was determined by ELISA,and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit.Results:Curcumin improved cardiac function,reduced fibrosis,restored miR-29b expression,and suppressed HDAC4 expression and activity in a dose-dependent manner.Furthermore,curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels,confirming reduced collagen synthesis.Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin.Conclusions:Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.
文摘目的探讨γ干扰素(interferon-gamma,INF-γ)、微小RNA-29a(microRNA-29a,miR-29a)、原癌基因PIM-1(proto-oncogene PIM-1,PIM-1)标志物在结核性胸膜炎合并胸腔积液中的表达水平变化及其与临床特征的关系。方法选取2021年5月—2023年6月在某医院就诊的107例结核性胸膜炎患者为研究对象,按照诊断结果分为结核性胸膜炎合并胸腔积液组(n=69)和单纯结核性胸膜炎组(n=38)。对比两组INF-γ、miR-29a、PIM-1表达水平差异,Spearman相关系数分析INF-γ、miR-29a、PIM-1表达水平与结核性胸膜炎合并胸腔积液的相关性;受试者操作特征(receiver operator characteristic,ROC)曲线分析INF-γ、miR-29a、PIM-1及其联合检测对结核性胸膜炎合并胸腔积液的预测效能,计量资料数据比较分析采用t检验,计数资料的比较采用χ^(2)检验。结果与单纯结核性胸膜炎组相比,结核性胸膜炎合并积液组的INF-γ(t=-5.440,P<0.001)、miR-29a(t=-3.561,P=0.001)、PIM-1(t=-3.232,P=0.002)均升高;Spearman相关系数分析显示,INF-γ、miR-29a、PIM-1表达水平与结核性胸膜炎合并胸腔积液呈正相关(r=0.443,P<0.001;r=0.332,P<0.001;r=0.291,P=0.002);ROC曲线显示,INF-γ、miR-29a、PIM-1单独及联合检测预测结核性胸膜炎合并胸腔积液的曲线下面积(area under the curve,AUC)分别为0.764、0.701、0.663和0.838,与INF-γ、miR-29a、PIM-1单独检测相比,联合检测对结核性胸膜炎合并胸腔积液具有较高的诊断效能(Z=1.983、2.168、2.859,P=0.047、0.030、0.004)。结论结核性胸膜炎合并胸腔积液患者INF-γ、miR-29a、PIM-1表达水平均表现为特异性的上调,这种联合检测对预测结核性胸膜炎患者是否合并胸腔积液具有良好的预测效能,值得临床推广应用。
