“两种不同中药”对大鼠心肌缺血基因表达的影响
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摘要
缺血性心脏病是严重危害人类的健康,其致病率和死亡率已超过肿瘤位居世界第一。心肌缺血后心脏发生显著的病理改变,包括炎症反应、自由基损伤、心肌细胞凋亡、细胞外基质沉积、心肌肥大和心室重构。这些病理改变可使心脏功能紊乱,最终导致心力衰竭。目前心肌缺血药物的研究仍存在明显的局限,本研究的目的就是评价姜黄素、杭白菊总黄酮对大鼠心肌缺血的疗效,并采用基因芯片技术对其可能的机制进行研究。
本研究分为两个部分,第一部分通过体内、体外两部分实验来评价姜黄素、杭白菊总黄酮对大鼠心肌缺血的治疗效果。采用H2O2致H9C2心肌细胞系损伤模型的方法,观察姜黄素、杭白菊总黄酮对心肌细胞氧化损伤的保护作用j采用结扎大鼠左冠状动脉前降支的方法造大鼠心肌缺血模型,造模72小时后以梗死面积、血流动力学、血清酶学相关指标评价姜黄素、杭白菊总黄酮对大鼠心肌缺血的保护作用；结果表明姜黄素在2μM时,对细胞氧化损伤有显著的保护作用(P<0.01),杭白菊总黄酮在64μg／mL范围内,对心肌细胞的损伤有显著的保护作用(P<0.01)；姜黄素、杭白菊总黄酮在大鼠缺血动物模型中可减少梗死面积,显著的改善血流动力学相关参数和血清中LDH和CK-MB的含量。
第二部分为探讨其可能的机制。方法是采用自制基因芯片检测造模后大鼠心脏相关基因的表达变化并观察给予姜黄素、杭白菊总黄酮治疗后大鼠心脏相关基因表达的改变；结果表明模型组对假手术组共筛选出了458个差异基因,姜黄素给药组对模型组筛选出297个差异基因,杭白菊总黄酮对模型组共筛选出61个差异基因。其中模型组／假手术组共涉及包括Toll-like receptor信号转导通路在内的27个典型信号转导通路；姜黄素／模型组的差异基因共涉及27个信号转导通路,包括其Cytokine-cytokine receptor interaction信号通路、JAK-STAT信号转导通路,Apoptosis信号转导通路等；杭白菊总黄酮组／模型组共涉及9条信号转导通路,包括Apoptosis信号转导通路、focal adhesion信号转导通路等。
Myocardial infarction (MI) is one of the important causes of mortality and morbidity in the world. In response to MI, the heart ventricle undergoes significantly pathological changes, such as inflammatory responses, free radical damage, myocardial apoptosis,extracellular matrix (EM) deposition, cardiac hypertrophy andventricular remodeling. These pathological changes eventually lead to cardiac dysfunction. The objective of this study was to evaluate whether Curcumin and total flavones from dendranthema morifolium (THP) was protective in myocardial ischemia and to determine the possible mechanisms of its protection.
This experiment contains two parts. The first part was to measure the protection of curcumin and THP. The model of H_2O_2 induced H9C2 cadiocyte injury was used to assess antioxidant effects of curcumin and THP, The rats which were exteriorized to ligate the proximal left anterior descending coronary artery were used to assess cardioprotective of curcumin and THP. Hemodynamic studies, infarct size and serum biochemical analysis was measured. The result showed that curcumin at 2μM has significantly antioxidant effect, the same as the THP at 64μg/mL. However, curcumin and THP could decress infract isze, ameliorate hemodynamic parameters, LDH and CK-MB contents of serum respectively.
The second part was to find the possible mechanisms of its function. Gene chips study was used. The result show that have 458 differently genes between model and sham, and 297 differently genes between curcumin and model, and 61 differently genes between THP and model. 27 pathways were significantly enriched for differentially expressedgenes between sham-operated and model group including Toll-like receptor signaling pathway, 27 pathways between curcumin group and model group including Cytokine-cytokine receptor interaction signaling pathway、JAK-STAT signaling pathway, Apoptosis signaling pathway, and 9 pathways between THP group and model group including Apoptosis signaling pathway and focal adhesion signaling pathway.
本研究分为两个部分,第一部分通过体内、体外两部分实验来评价姜黄素、杭白菊总黄酮对大鼠心肌缺血的治疗效果。采用H2O2致H9C2心肌细胞系损伤模型的方法,观察姜黄素、杭白菊总黄酮对心肌细胞氧化损伤的保护作用j采用结扎大鼠左冠状动脉前降支的方法造大鼠心肌缺血模型,造模72小时后以梗死面积、血流动力学、血清酶学相关指标评价姜黄素、杭白菊总黄酮对大鼠心肌缺血的保护作用；结果表明姜黄素在2μM时,对细胞氧化损伤有显著的保护作用(P<0.01),杭白菊总黄酮在64μg／mL范围内,对心肌细胞的损伤有显著的保护作用(P<0.01)；姜黄素、杭白菊总黄酮在大鼠缺血动物模型中可减少梗死面积,显著的改善血流动力学相关参数和血清中LDH和CK-MB的含量。
第二部分为探讨其可能的机制。方法是采用自制基因芯片检测造模后大鼠心脏相关基因的表达变化并观察给予姜黄素、杭白菊总黄酮治疗后大鼠心脏相关基因表达的改变；结果表明模型组对假手术组共筛选出了458个差异基因,姜黄素给药组对模型组筛选出297个差异基因,杭白菊总黄酮对模型组共筛选出61个差异基因。其中模型组／假手术组共涉及包括Toll-like receptor信号转导通路在内的27个典型信号转导通路；姜黄素／模型组的差异基因共涉及27个信号转导通路,包括其Cytokine-cytokine receptor interaction信号通路、JAK-STAT信号转导通路,Apoptosis信号转导通路等；杭白菊总黄酮组／模型组共涉及9条信号转导通路,包括Apoptosis信号转导通路、focal adhesion信号转导通路等。
Myocardial infarction (MI) is one of the important causes of mortality and morbidity in the world. In response to MI, the heart ventricle undergoes significantly pathological changes, such as inflammatory responses, free radical damage, myocardial apoptosis,extracellular matrix (EM) deposition, cardiac hypertrophy andventricular remodeling. These pathological changes eventually lead to cardiac dysfunction. The objective of this study was to evaluate whether Curcumin and total flavones from dendranthema morifolium (THP) was protective in myocardial ischemia and to determine the possible mechanisms of its protection.
This experiment contains two parts. The first part was to measure the protection of curcumin and THP. The model of H_2O_2 induced H9C2 cadiocyte injury was used to assess antioxidant effects of curcumin and THP, The rats which were exteriorized to ligate the proximal left anterior descending coronary artery were used to assess cardioprotective of curcumin and THP. Hemodynamic studies, infarct size and serum biochemical analysis was measured. The result showed that curcumin at 2μM has significantly antioxidant effect, the same as the THP at 64μg/mL. However, curcumin and THP could decress infract isze, ameliorate hemodynamic parameters, LDH and CK-MB contents of serum respectively.
The second part was to find the possible mechanisms of its function. Gene chips study was used. The result show that have 458 differently genes between model and sham, and 297 differently genes between curcumin and model, and 61 differently genes between THP and model. 27 pathways were significantly enriched for differentially expressedgenes between sham-operated and model group including Toll-like receptor signaling pathway, 27 pathways between curcumin group and model group including Cytokine-cytokine receptor interaction signaling pathway、JAK-STAT signaling pathway, Apoptosis signaling pathway, and 9 pathways between THP group and model group including Apoptosis signaling pathway and focal adhesion signaling pathway.
引文
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