黄芪多糖丹参酮对心衰大鼠心肌NF-κB通路过度激活及MIF表达的干预效应
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摘要
目的
建立心衰大鼠模型,通过从分子生物学和细胞因子网络调控体系的角度,初步探讨CHF时心肌中NF-κB信号转导通路过度激活的作用机制,分析其与MIF、TNF-α、IL-6、TGF-β1等细胞因子的相关性；验证中药单体黄芪多糖联合丹参酮-IIA对NF-κB信号转导通路过度激活的阻断效应；并且从气虚血瘀证-免疫调节失衡-多层次多靶点的研究角度,探索益气活血中药对心衰大鼠的干预效应,.开发中药抗炎免疫调节有效成分,为临床治疗CHF降低心血管疾病的住院率探索新思路、新方法。
方法
1.心力衰竭动物模型的制备：采用冠状动脉结扎术方法,经过第2周饲料减半,第3周游泳,第4周超声多普勒心电图,测定左心室舒张末期内径(LVEDD)、左心室舒张末期容积(LVEDV)、射血分数(EF),计算左室心脏指数CI,建立心衰模型。
2.分组与给药：将成模后大鼠纳入实验,分为黄芪多糖组(3g.kg-1.d-1,ig)、丹参酮组(5mg.kg-1.d-1,iv)、黄芪多糖+丹参酮组(剂量方法同上)、阿托伐他汀组(10mg.kg-1.d-1,ig)、模型组(等体积生理盐水,ig)、假手术组作为阴性对照(冠脉打虚结不结扎,从十二指肠予生理盐水,剂量方法同模型组),各用药组共干预6wk。
3.观察心肌病理形态学变化：将大鼠采血处死,摘取心尖部心肌组织依次固定、脱水、石蜡包埋,行苏木精-伊红(HE)染色,光镜观察并评分
4.免疫组织化学染色观察心肌组织NF-κB表达：采用图像分析系统半定量分析其表达量,并观察NF-κB激活时阳性表达核移位的情况。
5.应用RT-PCR法检测心肌NF-κB和MIFmRNA含量的变化,并在此方法检测的基础上,加用荧光实时定量PCR法,测定目的基因基础量。
6.采用Western blot法观察心肌NF-κB、IκB、IKK蛋白基因的表达,并采用LabWorks软件对图像进行灰度分析。
7.采用ELISA法测定血清MIF、TNF-α、IL-6及TGF-β1的水平,并分析其相关性。
8.应用SPSS17.0统计软件对数据进行分析处理。
结果
1.超声心动图结果显示,在术后第4周,对成模组大鼠和假手术组大鼠分别进行心脏超声检测,成模组大鼠的左心室舒张末期内径(LVEDD).左心室舒张末期容积(LVEDV)和射血分数(EF)均明显低于假手术组大鼠(P 2.病理形态学观察发现,模型组大鼠心肌核萎缩,室壁局部不规则,有坏死灶形成,心肌纤维数量减少,心肌横纹变浅,由胶原纤维形成的疤痕组织取代部分坏死灶,结缔组织增生明显,有大量炎性细胞的浸润；各用药组室壁破坏程度降低,残余心肌细胞增多,横纹较清晰,可见疤痕组织及少量炎细胞；与假手术组相比,模型组大鼠病理积分显著增高(P<0.05)；各用药组病理积分均明显下降,与模型组相比有显著性差异(P<0.05)；黄芪多糖+丹参酮组病理积分最低,与模型组相比具有显著性差异(P<0.05)。
3.免疫组化定量分析,结果显示心肌组织存在NF-κB不同程度的激活,与假手术组比较,模型组心肌组织NF-κB表达的阳性密度明显升高,差异有统计学意义(P<0.05)；与模型组比较,各用药组的阳性密度均明显降低(P<0.05)；配伍组的阳性密度与单一用药组相比,差异有统计学意义(P<0.05)。
4.RT-PCR法检测结果显示,模型组心肌NF-κB和MIFmRNA表达明显增高,各药物组对CHF大鼠心肌组织NF-κB和MIFmRNA表达有显著的抑制效应与假手术组相比,均具有显著性差异(P<0.05)；黄芪多糖丹参酮配伍组的蛋白表达与黄芪多糖组、丹参酮组相比,差异具有显著性(P<0.05)。
5.荧光实时定量PCR法结果显示,心肌组织NF-κB和MIFmRNA目的基因基础量分别为：假手术组(1)、(1),阿托伐他汀组(1.239)、(1.109),黄芪多糖+丹参酮组(1.453)、(1.515),黄芪多糖组(1.777)、(1.777),丹参酮组(1.986)、(2.219),模型组(2.345)、(2.602),提示各用药组NF-κB和MIFmRNA表达均显著降低,与假手术组相比具有显著性差异(P<0.05)；黄芪多糖丹参酮配伍组NF-κB和MIFmRNA表达与单一用药组相比,具有显著性差异(P<0.05)。
6.Western blot法检测心肌NF-κB、IκB、IKK的表达,结果显示：CHF模型组大鼠心肌组织NF-κB表达显著高于假手术组(P<0.05)；各用药组NF-κB表达均比模型组减少(P<0.05);配伍组NF-κB表达比单一用药组低(P<0.05)；然而,模型组心肌组织IκB、IκK表达比假手术组低(P<0.05)；各用药组IκB、IκK表达比模型组高(P<0.05)；配伍组IκB、IκK表达与单一用药组相比,明显增加,差异具有统计学意义(P<0.05)。
7.ELISA法检测血清MIF、TNF-α、IL-6及TGF-β1表达的影响：模型组大鼠血清MIF、TNF-α、IL-6水平分别为(5.94±2.14)(420.36±67.57)(3704.44±1048.81),明显高于假手术组(0.23±0.08)(53.96±3.18)(352.40±87.20),均有显著性差异(P 8.CHF大鼠血清MIF水平与血清TNF-α、IL-6和TGF-β1的相关性分析显示,血清MIF水平与血清TNF-α、IL-6呈正相关(r1=0.879,r2=0.904,P<0.01)；但是,TGF-β1与之趋势相反,血清MIF水平与血清TGF-β1呈负相关(r3=-0.602,P<0.01)。
结论
1.NF-κB作为信号传导途径中的枢纽,其激活途径主要与NF-κB由细胞质转运到细胞核内,同时伴随着抑制蛋白IKB及其最关键激酶IKK的降解呈负相关的密切关系,提示NF-κB信号转导通路在CHF发病中起重要作用。
2.MIF在CHF大鼠血清和心肌组织中的表达均明显增多,并且血清MIF与TNF-α和IL-6呈正相关,而与血清TGF-β1呈负相关,提示MIF作为上游细胞因子在CHF发病中起着重要的免疫调节作用。
3.黄芪多糖联合丹参酮-IIA的免疫调节治疗可纠正心衰大鼠的免疫状态调节炎症细胞因子与抗炎细胞因子间的平衡状态,具有明显的抗炎免疫调节活性,两者联用疗效优于单一用药组,对阻断大鼠心肌NF-κB转导通路过度激活及降低细胞因子MIF具有显著疗效,开发中药抗炎免疫有效成分的应用研究前景广阔。
Objective
From the perspective of molecular biology and cytokine network, the mechanism of the action on NF-κB signal transduction pathway may control the system of CHF,myocardial excessive activation on the correlation between the level of serum MIF,TNF-α,IL-6,TGF-β1; To verify Astragalus polysaccharide Tanshin-one IIA does excessive activaton on NF-κB signal transduction pathway.Point of view that Qi asthenia and stagnation of blood-immunoregulation, to explore the intervention effection on benefiting vital energy and activating blood circulation of traditional Chinese medicine; To explore the intervention and anti-inflammatory immune active ingredients, it may provide a new method to reduce cardiovascular hospitalization rates of CHF.
Method
1. To set up animal models of CHF:Used the coronary artery ligation method,decreased the feed a half after two weeks, swam after three weeks, and then were made ultrasound Doppler ECG after4weeks.
2. The SD rats were randomly divided into six experiment groups:APS group(3g.kg-1.d-1,ig),Tanshinone group(5mg.kg-1.d-1,iv),APS+Tanshinone group(dose as above),Atorvastatin group(10mg.kg-1.d-1,ig),model group(the volume of normal saline,ig),sham group as negative control(to play virtual nodes ligation of coronary artery,then were given normal saline to the duodenum by dose method),medicines were given for6wk.
3. Myocardial pathomorphology was observed by light microscope.
4. Immunohistochemistry was used to detect the expression of NF-κB in myocardial tissues.
5. The levels of NF-κB and MIFmRNA in the myocardial tissues were measured by RT-PCR and fluorescent real-time quantitative PCR method.
6. Western blot was used to detect the gene expression of NF-κB,IκB and IkK,and software LabWorks was used to analyze the gray image data.
7. the levels of MIF,TNF-α,IL-6and TGF-β1in the serum were measured and analyzed the correlation by ELISA.
8. SPSS17.0statistical software was used to analyze data.
Result
1. Echocardiography results showed that model group and sham group were detected by cardiac ultrasound after4weeks, respectively, left ventricular end-diastolic diameter(LVEDD),left ventricular end diastolicvolume(LVEDV) of model group were higher than sham group,and ejection fraction(EF) of model group was lower than sham group(P<0.01).
2. Pathological results showed that in model group there were many myocardial nuclear shrinking wall of local irregular, necrotic fociformation, decreased myocardial fibers,lighter myocardial stripes,and some necrosis replaced by collagenfiber formation of scar tissue,marked hyperplasia of connective tissues, large inflammatory cell infiltration; Remarks of medication groups wall damage decreased,increased residual myocardial cells,clearer stripes,visible scar tissue and inflammatory cells;Pathologic score of model group was higher increased than sham group(P<0.05);Pathologic scores of medication groups were significantly lower than those of model group(P<0.05); Remark of APS+Tan group was the lowest(P<0.05).
3. Immunohistochemistry showed that the expression of NF-κB in model group was higher than sham group(P<0.05); that of medication groups were lower than that of model group(P<0.05);that of matching group was lower than that of single medication group(P<0.05).
4. RT-PCR assay results showed that the expressions of NF-κB and MIFmRNA in model group were significantly higher than medication groups; medication groups had much more inhibition than sham group(P<0.05); those of matching group were lower than those of single medication group(P<0.05).
5. Fluorescent real-time quantitative PCR results show that the target gene basis of NF-κB and MIFmRNA:sham group(1),(1); Atorvastatin group(1.239),(1.109); APS+Tan group(1.453),(1.515); APS group(1.777),(1.777); Tan group (1.986),(2.219); model group(2.345),(2.602); those of medication groups decreased significantly than sham group(P<0.05); those of APS+Tan matching group were lower than those of single medication group(P<0.05).
6. Western blot showed that the expression of NF-κB in model group was significantly higher than sham group(P<0.05); that of medication groups was lower than model group(P<0.05); that of matching group was lower than single medication group(P<0.05); but on the contrary,the expressions of IκB、IκK in model group were lower than sham group(P<0.05).
7. The levels of MIF,TNF-α,IL-6in the serum by ELISA showed that those of model group were(5.94±2.14),(420.36±67.57),(3704.44±1048.81),which were higher than sham group(0.23±0.08),(53.96±3.18),(352.40±87.20)(P<0.05); those of medication groups were significantly lower than those of model group(P<0.05). but on the contrary,the level of serum TGF-β1showed an opposite tendency.
8. Analysis of correlation between serum MIF、TNF-α、IL-6by ELISA showed that those of medication groups decreased significantly,and the level of serum MIF was positively correlated with those of serum TNF-α and IL-6(r1=0.879,r2=0.904, P<0.05),but the level of serum MIF was negative correlated with that of TGF-β1(r3=-0.602,P<0.05).
Conclusions
1. NF-κB as a hub in the signal transduction pathway released into the nucleus after activation,and accompanied by inhibition of IκB and degradation of most critical kinase IκK, all of which can suggest that NF-κB signal transduction pathway play an important role in CHF incidence.
2. The levels of MIF in the serum and myocardial tissues of CHF rats significantly enhanced, and the expression of MIF, TNF-α and IL-6showed a positive correlation, but negatively correlation with those of serum TGF-β1, suggesting that as an upstream cytokine,MIF plays a key immunomodulatory role on onset of CHF.
3. Astragalus polysaccharide joint Tanshinone-ⅡA immunomodulatory therapy can correct the immune status of CHF rats,regulating the equilibrium between inflammatory and anti-inflammatory cytokines,possessing significant anti-inflammatory and immunocompetence activity.Those of matching group were more effective than single medication group, blocking the overactivation of NF-κB transduction pathway,and MIF has shown a significant therapeutic curative effection.This study can provide a broaden prospect for anti-inflammatory immune and active ingredients of the traditional Chinese medicine in treating CHF.
建立心衰大鼠模型,通过从分子生物学和细胞因子网络调控体系的角度,初步探讨CHF时心肌中NF-κB信号转导通路过度激活的作用机制,分析其与MIF、TNF-α、IL-6、TGF-β1等细胞因子的相关性；验证中药单体黄芪多糖联合丹参酮-IIA对NF-κB信号转导通路过度激活的阻断效应；并且从气虚血瘀证-免疫调节失衡-多层次多靶点的研究角度,探索益气活血中药对心衰大鼠的干预效应,.开发中药抗炎免疫调节有效成分,为临床治疗CHF降低心血管疾病的住院率探索新思路、新方法。
方法
1.心力衰竭动物模型的制备：采用冠状动脉结扎术方法,经过第2周饲料减半,第3周游泳,第4周超声多普勒心电图,测定左心室舒张末期内径(LVEDD)、左心室舒张末期容积(LVEDV)、射血分数(EF),计算左室心脏指数CI,建立心衰模型。
2.分组与给药：将成模后大鼠纳入实验,分为黄芪多糖组(3g.kg-1.d-1,ig)、丹参酮组(5mg.kg-1.d-1,iv)、黄芪多糖+丹参酮组(剂量方法同上)、阿托伐他汀组(10mg.kg-1.d-1,ig)、模型组(等体积生理盐水,ig)、假手术组作为阴性对照(冠脉打虚结不结扎,从十二指肠予生理盐水,剂量方法同模型组),各用药组共干预6wk。
3.观察心肌病理形态学变化：将大鼠采血处死,摘取心尖部心肌组织依次固定、脱水、石蜡包埋,行苏木精-伊红(HE)染色,光镜观察并评分
4.免疫组织化学染色观察心肌组织NF-κB表达：采用图像分析系统半定量分析其表达量,并观察NF-κB激活时阳性表达核移位的情况。
5.应用RT-PCR法检测心肌NF-κB和MIFmRNA含量的变化,并在此方法检测的基础上,加用荧光实时定量PCR法,测定目的基因基础量。
6.采用Western blot法观察心肌NF-κB、IκB、IKK蛋白基因的表达,并采用LabWorks软件对图像进行灰度分析。
7.采用ELISA法测定血清MIF、TNF-α、IL-6及TGF-β1的水平,并分析其相关性。
8.应用SPSS17.0统计软件对数据进行分析处理。
结果
1.超声心动图结果显示,在术后第4周,对成模组大鼠和假手术组大鼠分别进行心脏超声检测,成模组大鼠的左心室舒张末期内径(LVEDD).左心室舒张末期容积(LVEDV)和射血分数(EF)均明显低于假手术组大鼠(P
3.免疫组化定量分析,结果显示心肌组织存在NF-κB不同程度的激活,与假手术组比较,模型组心肌组织NF-κB表达的阳性密度明显升高,差异有统计学意义(P<0.05)；与模型组比较,各用药组的阳性密度均明显降低(P<0.05)；配伍组的阳性密度与单一用药组相比,差异有统计学意义(P<0.05)。
4.RT-PCR法检测结果显示,模型组心肌NF-κB和MIFmRNA表达明显增高,各药物组对CHF大鼠心肌组织NF-κB和MIFmRNA表达有显著的抑制效应与假手术组相比,均具有显著性差异(P<0.05)；黄芪多糖丹参酮配伍组的蛋白表达与黄芪多糖组、丹参酮组相比,差异具有显著性(P<0.05)。
5.荧光实时定量PCR法结果显示,心肌组织NF-κB和MIFmRNA目的基因基础量分别为：假手术组(1)、(1),阿托伐他汀组(1.239)、(1.109),黄芪多糖+丹参酮组(1.453)、(1.515),黄芪多糖组(1.777)、(1.777),丹参酮组(1.986)、(2.219),模型组(2.345)、(2.602),提示各用药组NF-κB和MIFmRNA表达均显著降低,与假手术组相比具有显著性差异(P<0.05)；黄芪多糖丹参酮配伍组NF-κB和MIFmRNA表达与单一用药组相比,具有显著性差异(P<0.05)。
6.Western blot法检测心肌NF-κB、IκB、IKK的表达,结果显示：CHF模型组大鼠心肌组织NF-κB表达显著高于假手术组(P<0.05)；各用药组NF-κB表达均比模型组减少(P<0.05);配伍组NF-κB表达比单一用药组低(P<0.05)；然而,模型组心肌组织IκB、IκK表达比假手术组低(P<0.05)；各用药组IκB、IκK表达比模型组高(P<0.05)；配伍组IκB、IκK表达与单一用药组相比,明显增加,差异具有统计学意义(P<0.05)。
7.ELISA法检测血清MIF、TNF-α、IL-6及TGF-β1表达的影响：模型组大鼠血清MIF、TNF-α、IL-6水平分别为(5.94±2.14)(420.36±67.57)(3704.44±1048.81),明显高于假手术组(0.23±0.08)(53.96±3.18)(352.40±87.20),均有显著性差异(P
结论
1.NF-κB作为信号传导途径中的枢纽,其激活途径主要与NF-κB由细胞质转运到细胞核内,同时伴随着抑制蛋白IKB及其最关键激酶IKK的降解呈负相关的密切关系,提示NF-κB信号转导通路在CHF发病中起重要作用。
2.MIF在CHF大鼠血清和心肌组织中的表达均明显增多,并且血清MIF与TNF-α和IL-6呈正相关,而与血清TGF-β1呈负相关,提示MIF作为上游细胞因子在CHF发病中起着重要的免疫调节作用。
3.黄芪多糖联合丹参酮-IIA的免疫调节治疗可纠正心衰大鼠的免疫状态调节炎症细胞因子与抗炎细胞因子间的平衡状态,具有明显的抗炎免疫调节活性,两者联用疗效优于单一用药组,对阻断大鼠心肌NF-κB转导通路过度激活及降低细胞因子MIF具有显著疗效,开发中药抗炎免疫有效成分的应用研究前景广阔。
Objective
From the perspective of molecular biology and cytokine network, the mechanism of the action on NF-κB signal transduction pathway may control the system of CHF,myocardial excessive activation on the correlation between the level of serum MIF,TNF-α,IL-6,TGF-β1; To verify Astragalus polysaccharide Tanshin-one IIA does excessive activaton on NF-κB signal transduction pathway.Point of view that Qi asthenia and stagnation of blood-immunoregulation, to explore the intervention effection on benefiting vital energy and activating blood circulation of traditional Chinese medicine; To explore the intervention and anti-inflammatory immune active ingredients, it may provide a new method to reduce cardiovascular hospitalization rates of CHF.
Method
1. To set up animal models of CHF:Used the coronary artery ligation method,decreased the feed a half after two weeks, swam after three weeks, and then were made ultrasound Doppler ECG after4weeks.
2. The SD rats were randomly divided into six experiment groups:APS group(3g.kg-1.d-1,ig),Tanshinone group(5mg.kg-1.d-1,iv),APS+Tanshinone group(dose as above),Atorvastatin group(10mg.kg-1.d-1,ig),model group(the volume of normal saline,ig),sham group as negative control(to play virtual nodes ligation of coronary artery,then were given normal saline to the duodenum by dose method),medicines were given for6wk.
3. Myocardial pathomorphology was observed by light microscope.
4. Immunohistochemistry was used to detect the expression of NF-κB in myocardial tissues.
5. The levels of NF-κB and MIFmRNA in the myocardial tissues were measured by RT-PCR and fluorescent real-time quantitative PCR method.
6. Western blot was used to detect the gene expression of NF-κB,IκB and IkK,and software LabWorks was used to analyze the gray image data.
7. the levels of MIF,TNF-α,IL-6and TGF-β1in the serum were measured and analyzed the correlation by ELISA.
8. SPSS17.0statistical software was used to analyze data.
Result
1. Echocardiography results showed that model group and sham group were detected by cardiac ultrasound after4weeks, respectively, left ventricular end-diastolic diameter(LVEDD),left ventricular end diastolicvolume(LVEDV) of model group were higher than sham group,and ejection fraction(EF) of model group was lower than sham group(P<0.01).
2. Pathological results showed that in model group there were many myocardial nuclear shrinking wall of local irregular, necrotic fociformation, decreased myocardial fibers,lighter myocardial stripes,and some necrosis replaced by collagenfiber formation of scar tissue,marked hyperplasia of connective tissues, large inflammatory cell infiltration; Remarks of medication groups wall damage decreased,increased residual myocardial cells,clearer stripes,visible scar tissue and inflammatory cells;Pathologic score of model group was higher increased than sham group(P<0.05);Pathologic scores of medication groups were significantly lower than those of model group(P<0.05); Remark of APS+Tan group was the lowest(P<0.05).
3. Immunohistochemistry showed that the expression of NF-κB in model group was higher than sham group(P<0.05); that of medication groups were lower than that of model group(P<0.05);that of matching group was lower than that of single medication group(P<0.05).
4. RT-PCR assay results showed that the expressions of NF-κB and MIFmRNA in model group were significantly higher than medication groups; medication groups had much more inhibition than sham group(P<0.05); those of matching group were lower than those of single medication group(P<0.05).
5. Fluorescent real-time quantitative PCR results show that the target gene basis of NF-κB and MIFmRNA:sham group(1),(1); Atorvastatin group(1.239),(1.109); APS+Tan group(1.453),(1.515); APS group(1.777),(1.777); Tan group (1.986),(2.219); model group(2.345),(2.602); those of medication groups decreased significantly than sham group(P<0.05); those of APS+Tan matching group were lower than those of single medication group(P<0.05).
6. Western blot showed that the expression of NF-κB in model group was significantly higher than sham group(P<0.05); that of medication groups was lower than model group(P<0.05); that of matching group was lower than single medication group(P<0.05); but on the contrary,the expressions of IκB、IκK in model group were lower than sham group(P<0.05).
7. The levels of MIF,TNF-α,IL-6in the serum by ELISA showed that those of model group were(5.94±2.14),(420.36±67.57),(3704.44±1048.81),which were higher than sham group(0.23±0.08),(53.96±3.18),(352.40±87.20)(P<0.05); those of medication groups were significantly lower than those of model group(P<0.05). but on the contrary,the level of serum TGF-β1showed an opposite tendency.
8. Analysis of correlation between serum MIF、TNF-α、IL-6by ELISA showed that those of medication groups decreased significantly,and the level of serum MIF was positively correlated with those of serum TNF-α and IL-6(r1=0.879,r2=0.904, P<0.05),but the level of serum MIF was negative correlated with that of TGF-β1(r3=-0.602,P<0.05).
Conclusions
1. NF-κB as a hub in the signal transduction pathway released into the nucleus after activation,and accompanied by inhibition of IκB and degradation of most critical kinase IκK, all of which can suggest that NF-κB signal transduction pathway play an important role in CHF incidence.
2. The levels of MIF in the serum and myocardial tissues of CHF rats significantly enhanced, and the expression of MIF, TNF-α and IL-6showed a positive correlation, but negatively correlation with those of serum TGF-β1, suggesting that as an upstream cytokine,MIF plays a key immunomodulatory role on onset of CHF.
3. Astragalus polysaccharide joint Tanshinone-ⅡA immunomodulatory therapy can correct the immune status of CHF rats,regulating the equilibrium between inflammatory and anti-inflammatory cytokines,possessing significant anti-inflammatory and immunocompetence activity.Those of matching group were more effective than single medication group, blocking the overactivation of NF-κB transduction pathway,and MIF has shown a significant therapeutic curative effection.This study can provide a broaden prospect for anti-inflammatory immune and active ingredients of the traditional Chinese medicine in treating CHF.
引文
[1]Baig MK,Mahon N,Mckemna WJ,et al.The pathophysiology of advanced heart failure[J].Am Heart J,1998,135(suppl):S216-230.
[2]Singh H,Sen R,Baltimore D,et al.A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes.Nature.1986 Jan9-15;319 (6049):154-8.
[3]Valen G,Yan ZQ,Hanson GK.Nuclear factor kappa-B and the heart[J].J Mol Cell Caridial,2001,38(2):307-314.
[4]曹雪涛.免疫学前沿进展,北京：人民卫生出版社,2009,3,第1版,637
[5]Siebenlist U,Franzoso G,Brown K.Structure regulation and function of NF-kappaB [J].Annu Rev Cell Biol,1994,10(2):405-455.
[6]杨敏烈.核因子-κB的作用及在心血管疾病治疗中的研究进展.南通大学学报(医学版),2008,28(1)：77-79.
[7]Vandermeeren M,et al.Dimethylfumarate is an inhibitor of cytokine induced E-selection,VCAM-1 and ICAM-1 expression in human endothelial cells[J].Biochem Biophys Res Commun,1997,234(1):19-23.
[8]Finco TS,Baldwin AS.Mechanistic aspects of NF-κB regulation:the emerging role of phosphorylation and proteolysis[J].Immunity,1995,3:263-272.
[9]Anlonella E,Janko W,Anna C,et al.The activation of the NF-κB system in chronic heart failure[J].J Am Coll Cardiol.2003,41:157-162.
[10]Anversa P,Nadal GB.Myocyte renewal and ventricular remodeling[J].Nature,2002, 415:240-243.
[11]Yndestad A,Damas JK,FieE,et al.Role of inflammation in the progression of heart failure[J].Curr Cardiol Rep,2007,3:236-241.
[12]Frantz S,Fraccarollo D,Wagner H,et al.Sustained activation of nuclear factor kappaB and activator protein-lin chronic heart failure,Cardiovasc Res,2003,57:749-756.
[13]Ogawa K,Hirooka Y,Kishi T,et al.Brain AT1 receptor activates the sympathetic nervous system through toll-like receptor-4 in mice with heart failure[J],J Cardiovasc Pharmacol,2011Nov;58(5):543-9.
[14]Siednienko J,Jankowska EA,Banasiak W,et al.Nuclear factor-kappaB activity in peripheral blood mononuclear cells in cachectic and non-cachectic patients with chronic heart failure.Int J Cardiol,2007,Nov15;122(2):111-6.Epub,2007,Jan30.
[15]LuzzaF,BruniF,RizzoF,et al Pathophysiology of congestive heart failure.Minerva Cardioangiol,2002,50:209-219.
[16]Deswal A,Petersen NJ,Feldman AM,et al. Cytokines and cytokine receptors in advanced heart failure:an analysis of the cytokine database from the Vesanrinone Trial(VEST)[J].Circulation,2001,103(11):2055-2059.
[17]Jones WK,Brown M,Ren X,et al.NF-kappa B as an integrator of diverse signaling pathways:the heart of myocardial signaling?Cardiovasc Toxicol,2003,3:229-254.
[18]Greenberg BJ,Treatment of heart failure state of the art and prospectives[J]. Cardiovasc Pharmacol,2001,38:59-63.
[19]Martinez RM.Cardiac remodeling and inflammation[J].Arch Cardiol Mex,2006,76: 58-66.
[20]戴闰柱.世纪之交的心力衰竭[J].中华心血管病杂志,2001,29(11)：641-3.
[21]ChandrashekharY.Role of apoptosis in ventricular remodeling[J].Curr Heart Fail Rep,2005,2(1):18-22.
[22]Toth MJ,Ades PA.Tischler MD,et al.Immune activation is associated with reducted skeletal muscle mass and physical function in chronic heart failure[J].Int J Cardiol,2005,14: 85-87.
[23]Frantz S,FraccarlloD,Wagner H,et al.Sustained activation of nuclear factor kappaB and activator protein-1 in chronic heart failure[J].Cardiovasc Rec,2003,57:749-756.
[24]Matsumori A,Anti-inflammatory therapy for heart failure[J].Current Opinion in Phamacology,2004,4:126.
[25]Li YY,Feng YG,Kadokami T,et al.Myocardial extracellure matrix remodeling in transgenic mice overexpressing tumor necrosis factor alpha can be modulated by anti-tumor necrosis factor alpha therapy[J].Proc Natl Acad Sci USA,2000,97(4):H12746-51.
[26]Spinale FG. Matrix metalloproteinases regulation and dysregulation in the falling heart[J].Circ Res,2002,90(2):520-530.
[27]朱茵,贾如意,高佩增.冠心病心力衰竭患者血清NF-KB水平变化及意义.山东医药,2010,50(23)：7-9.
[28]Ojamaa K.Signaling mechanisms in thyroid hormone-induced cardiac hypertrophy. Vascul Pharmacol.2009,Dec11.
[29]Alvarez-Guardia D,Palomer X,Coll T,et al.The p65 subunit of NF-{kappa)B binds to{alpha},linking inflammation and metabolic disturbances in cardiac cells, Cardiovasc Rs, 2010,Mar 30.
[30]Kumar S,Seqqat R.Chigurupati S,et al.Inhibition of nuclear factor-κB regresse cardiac hypertrophy by modulating the expression of extracellular matrix and adhesion molecules.Free Radic Biol,Med 2011 Jan 1:50(1):206-215.
[31]WongSC,Fukuchi M,Melnyk P,et al.Induction of cyclooxgenase-2 and activation of nuclear factor kappa B in myocardium of patints with congestive heart failure[J].Circulation, 1998,98(2):100-103.
[32]Cook SA,Novikoy MS,Ahn Y,et al.A20 is dynamically regulated in the heart and inhibitis the hypertrophic response[J].Circulation,2003,108:664-67.
[33]PurcellNH,Tang G,Mercuio F,et al.Activation of NF-κB is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes[J].Proc Natl Acad Sci USA,2001, 98:6668-6673.
[34]Gupta S,Purcell NH,Lin A,et al. Activation of nuclar factor-κB is necessary for myotrophin induced cardiac hypertrophy[J].J Cell Biol,2002,159:1019-28.
[35]Higuchi Y,Otsu K,Nishida K,et al.Involvement of reactive oxygen species mediated NF-κB activation in TNF-a induced cardiomyocyte hypertrophy[J].J Mol Cell Cardiol,2002, 34:233-240.
[36]Hirotani S,Otsu K,Nishida K,et al.Involvement of nuclear factor-KB and apoptosis signal regulating kinase-1 in Gprotein coupled receptor agonist induced cardiomyocyte hypertrophy [J].Circulation,2002,105,509-515.
[37]Fritzenwanger M,Foerster M,Meusel K,et al.Cardiotrophin-1 induces intercellular adhesion molecule-1 expression by nuclear factor kappa-B activation in human umbilical vein endothelial cells.Chin Med J(Engl).2008Dec,20;121(24):2592-8.
[38]Yuehua Li,Tuanzhu Ha. NF-κB activation is required for the development of cardie hypertrophy invivo[J].Am J Physiol Heart Circ Physiol,2004,287IH1712-20.
[39]De KeulenaerGW,Wang Y,Feng Y,et al.Identification of IEX-1 as a biomechanically controlled nuclear factor-κB target gene that inhibits cardiomyocyte hypertrophy[J].Circ Res,2002,90:690-696.
[40]Chen G,Zhou X,FloreaS,et al.Expression of active protein phosphatase-1,inhibitor-1 attenuates chronic beta-agonist-induced cardiac apoptosis.Basic Res Cardiol,2010,May 30.
[41]Monaco C,Paleolog E.Nuclear factor-κB:a potential therapeutic target in atheroscle-rosis and thrombosis[J].Cardiovasc Res,2004,61:671-682.
[42]Matsushita H,Morishita R,Nata T,et al.Hypoxia induced endothelial apoptosis through nuclear factor-kappaB mediated bcl suppression:in vivo evidence of the importance of NF-kappaB in endothelial cell regulation[J].Circ Res,2000,86(9):974-981.
[43]Matsumori A,Sasayama S.The role of inflammatory mediators in the failing heart: immunomodulation of cytokines in experimental models of heart failure[J].Heart Rev Fail, 2001,6(2):129-136.
[44]Chanani NK,Cowan DB,Takeuchi K,et al.Differential effects of amrinone and milrinone upon myocardial inflammatory signaling[J].Circulation,2002,106:1284-1289.
[45]Bhatt DL,Topol EJ.Need to test the arterial inflammation hypothesis[J].Circula-tion,2002,106:136-140.
[46]Ito H,Ono k,Nishio R,et al.Amiodarone inhibits interleukin-6 production and attenuates myocardial injury induced by viral myocarditis in mice[J].Cytokine hypertro-phy.2002,17:197-202.
[47]Mizuochi Y,Okajima K,Harada N,et al.Carvedilol,a nonselective beta-blocker, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro,Transl Res Apr,2007,Transl Apr;149(4):223-230.
[48]许锦荣,陈玲,曾坚,等.老年心力衰竭患者核因子-κB与心功能的关系,实用医学杂志,2009,25(13)：2080-2081.
[1]中华人民共和国卫生部药典委员会汇编.中华人民共和国药典(2005年版)一部[S].北京：化学工业出版社,2005,52-53.
[2]中华本草精选本/家中医药管理局《中华本草》编委会.—上海：上海科学技术出版社,1998,1(2009,5重印)：1653,1669.
[3]赵娜,郭治昕,赵雪,等.丹参的化学成分与药理作用[J].国外医药：植物药分册,2007,22(4)：155-160.
[4]叶勇.丹参有效成分分离的研究进展[J].药品评价,2005,2(2)：146-8,118
[5]中国医学科学院.中草药现代研究(第二册)[M].北京：北京医科大学、中国协和医科大学联合出版社,1996,50
[6]陈丽娜,朱晓新.丹参改善血液流变性的实验研究进展,中国中药杂志,2005,30(8)：630-633，640.
[7]蔡丽萍,习志刚,杨虹.丹参酮的药理作用和临床研究进展.广东药学院学报,2008,24(3)：321-4.
[8]王维婷,单成钢,倪大鹏,等.丹参有效成分代谢生理生化及分子生物学研究进展.中药材,2009,32(9)：1472-1476.
[9]梁雪丹,范田园,郑颖.以丹参素为指标成分的丹参制剂及其药动学研究概述.中国新药杂志,2008,17(21)：1838-1842.
[10]陈彦贾,晓斌,施亚芳,等.不同提取方法测定丹参药材中丹参素的含量的比较研究[J].江苏中医药,2003,24(6)：55-56.
[11]贾娜,项海芝,杨松松.丹参水溶性部分丹酚酸的进展述评.辽宁中医学院学报,2006,8(3)：41-42.
[12]张中堂,张群林,张云静,等.中药丹参有效成分的提取分离方法研究进展.时珍国医国药,2010,21(3)：728-730.
[13]龚丽娅,郑智,熊玮,等.丹参酮ⅡA抑制血管紧张素Ⅱ诱导的大鼠心肌细胞肥大[J].华西医学杂志,2004,19(1)：24-27.
[14]杨志霞,林谦,农一兵,等.黄芪多糖联合丹参酮对心衰大鼠心肌NF-κB通路过度激活的影响[J].北京中医药大学学报,2011,34(9)：609-612.
[15]范慧霞,药丹参药理作用研究概况[J].新疆中医药,2007,25(5)：113-6.
[16]Fu JJ, Huang H, Liu J,et al.TanshinoneⅡA protects cardiac myocytes against oxidative stress-triggered damage and apoptosis[J].Euro J Pharmacol,2007,568(1-3):213-221.
[17]YangR,LiuA,MaX,et al. Sodium tanshinone IIA sulfonate protects cardiomyocytes against oxidative stress-mediated apoptosis through inhibiting JNK activation[J]. J Cardiovasc Pharmacol,2008,51(4):396-401.
[18]Liu YL,Liu GT.Inhibition of human low-density lipoprotein by salviano licacid-A[J]. Atca Phar Sin,2002,37(2):81-85.
[19]吴立玲.缺血-再灌注损伤[M],//金惠铭,王建枝.病理生理学.第6版,北京：人民卫生出版社,2004,205
[20]朱立民,曾秋棠.丹参酮IIA磺酸钠对家兔在体外单相动作电位影响的研究[J].山东医药,2005,45(20)：22-23.
[21]梁文,曹西南.丹参在心脏保存中应用的研究进展,医学综述,2009,15(13)：2015-6.
[22]张洁,曾晓荣,杨艳,等.丹参酮HA磺酸钠和丹参素对猪冠状动脉平滑肌细胞钙激活钾通道的激活机制[J].中国药理学与毒理学杂志,2005,19(4)：270-273.
[23]邓惠英.丹参及其有效成份的药理研究概况.现代医药卫生,2007,23(12)：1812-3.
[24]刘光喜,黄韵诗.丹参对心血管作用的研究进展,中医药导报,2008,14(3)：86-88.
[25]高枫,孙桂波,聂媛媛,等.丹酚酸B对大鼠离体工作心脏血流动力学的影响,中国实验动物学报,2011,19(5)：396-399.
[26]郭伟强,曹婷婷,徐雯婧,等.丹参酮IIA对细胞因子IL6和IL-10的影响[J].技术,2008,18(6)：30-32.
[27]Miettinen KH,Lassus J,H arjola VP,et al.Prognosticrole of pro-and anti-inflammat-ory cytokines and the irpolym orphisms in acute decompensated heart failure[J].EurHeart Fail,2008,10(4):396-403.
[28]RoncoC.HaapioM,House AA,et al.Cardiorenal syndrome[J].Am Coll Cardiol,2008, 52(19):1527-1539.
[29]廖晓春,刘文举,扬海玉.丹参酮IIA磺酸钠对心肾综合征患者肾小球滤过率的影响[J].湖南中医药大学学报,2009,29(11)：23-24.
[30]Jang SI,Kim HJ,Kim YJ,et al.Tanshinone IIA inhibits LPS induced NF-κB activation in Raw 264.7 cells possible involvement of the NIK-IKK, EPK1/2,p38 and JNK pathways[J].Eur J Pharmacol,2006,542(1-3):1-7.
[31]齐艳艳,史永照.丹参对缺血再灌注损伤的保护作用及机制研究进展.上海中医药大学学报,2010,24(2)：89-91.
[32]陈树彤,史培杰,黄电波.复方丹参滴丸治疗冠心病合并高血脂症疗效观察[J].医学理论与实践,2007,2(7)：750-752.
[33]马海燕.低分子肝素联合丹参酮注射液治疗不稳定型心绞痛疗效观察,医学理论与实践,2010,23(12)：1455-1456.
[34]冯俊,张洁,郑智,等.丹参酮IIA抑制新生大鼠心肌细胞肥大的作用机制.中国急救医学,2006,26(14)：274-276.
[35]宋利,陶新为,钟晓辉.中药辅助治疗冠心病慢性心力衰竭41例.中国实用医 药,2009,4(24)：44-45.
[36]马晨,张善飞,曹彦光,等.丹参注射液对离体大鼠心肌能量代谢的调节作用.中国药科大学学报,2009,40(2)：147-151.
[37]Miodor.Generation of free radicals and/or active oxygen by light or irra diation of hydrogen peroxide or sodium hypochlorite[J].J Endod,2003,29(2):141-143.
[38]李湘平,尹桃.丹参多酚酸盐注射液治疗冠心病的疗效观察.中国现代医学杂志,2010,20(4)：619-621,624
[39]国家药典委员会.中华人民共和国药典临床用药须知中药卷[M].北京：人民卫生出版社,2005,331.
[40]刘孝蓉.复方丹参注射液联合酚妥拉明治疗肺心病心衰疗效观察.现代医药卫生,2010,26(19)：2906-2907.
[41]史载祥,汪燕,杜金行,等.丹参粉针联合西药治疗冠心病心绞痛临床观察.中国中医急症,2010,(6)：911-912.
[1]Hunt SA,Abraam WT,Chin MH,et al.ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult,Circulation,2005,112: 154-235.
[2]MartinezRM.Cardiac remodeling and inflammation[J].Arch CardiolMex,2006,76: S58-66.
[3]Katsuyamai L,Hirata Y,et al,derivative inhibits cytokine induced OS plessioii and NF-kappa B activation by preventing pho6phoryhtlon and degradation of kappaB-alpha OJJ Biochem(Tokyo),2001,129:585-591.
[4]Monsuez JJ,Escaut L,Teicher E,et al.Cytokines in HIV-associated cardiomyopathy, Int J Cardiol.2007 Aug 21; 120(2):150-157.
[5]Li Y,Ha T,Gao X,et al.NF-KB activation is required for the development of cardiac hypertrophy in vivo[J].Ant J Physiol Heart Circ Physiol,2004,287(4):H1712-1720.
[6]杨志霞,林谦,马利,等.黄芪多糖丹参酮对慢性心衰大鼠MIF表达的调控作用[J],中国药理学通报,2011,27(9)：1214-1217.
[7]杨志霞,林谦,农一兵,等.黄芪多糖联合丹参酮对心衰大鼠心肌NF-κB通路过度激活的影响[J].北京中医药大学学报,2011,34(9)：609-612.
[8]杨海波,李振民,阚秀莲,等.黄芪对慢性心力衰竭患者左室重构的影响[J].中西医结合心脑血管病杂志,2009,8(9)：1031-1032.
[9]谢鸣.中医方剂现代研究[M].北京：学苑出版社,1997：1034.
[10]朱嘉蓉,罗厚蔚.丹参酮Ⅱ的抑菌活性研究[J].中国药科大学学报,2004,35(4)：368
[1]Deten A,Holzl A,Leicht M,et al.Changes in extracellular matrix and in transforming growth factor beta isoforms after coronary artery ligation in rats[J].J Mol Cell Cardiol,2001, Jun;33(6):1191-1207.
[2]Gurgel CAS,Ramos EAG,Azevedo RA,et al.Expression of Ki-67,p53 and p63 proteins in keratocyst odontogenic tumours:an immunohistochemical study.J Mol Hist,2008,39:311-316.
[3]WongML,MedranoJF.Real-time PCR for mRNA quantitation[J].Biotechniques,2005, 39:75-85.
[1]李晓娜.益气活血法治疗心力衰竭近况,甘肃中医,2009,22(2)：16-17.
[2]傅向华,孙家安.心力衰竭的现代认识[J].床荟萃,2004,19(1)：55-58.
[3]解海宁,张艳,胡晓红,等.气虚血瘀水停在慢性心衰实质研究探讨.中华中医药学刊,2007,12(25)：2603-2604.
[4]严夏,李俊,方志坚,等.温阳活血法治疗慢性充血性心力衰竭的临床研究[J].上海中医药杂志,2005,39(8)：17-18.
[5]李小平.中药分期辩证治疗慢性充血性心力衰竭63例[J].陕西中医,2006,27(7)：775-776.
[6]戴霞.充血性心力衰竭的中医研究概况[J].北京中医,2005,24(1)：47
[7]周鲁,宋航.中药复方治疗充血性心力衰竭的用药分析[J].时珍国医国药,2005,16(3)：185-186.
[8]黄峻.心力衰竭治疗的现状和进展,岭南心血管病杂志,2010,16(2)：85-88.
[9]徐梦丹,戴秋燕.上海交通大学(医学版),2009,29(6)：649-653.
[10]张长军,于凤琴,徐淑玲,等.足月新生儿缺氧缺血性脑病与低钙血症[J].中国妇幼保健,2005,20(10)：1240-1241.
[11]吴晓光.细胞因子与心力衰竭关系的研究进展.中华保健医学杂志.2008,10(1)：72.
[12]Hirota H,Izumi M,Hamaguchi T,et al.Circulation interleukin-6 family cytokine and their receptors in patients with congestive heart failure [J].Heart Vssels,2004,19(5):237-241.
[13]傅广,赵水平.心力衰竭患者TNF-a和IL-6的变化及氯沙坦的影响[J].中国循环杂志,2005,16(4)：243-251.
[14]Gupfa S,Sen S.Role of the NF-kappaB signaling cascade and NF-kappaB targeted genes in failing human hearts.J MolMed,2005,83:993-1004.
[15]黄涌,阮经文,杨春涛,等.依达拉奉保护Hgc2心肌细胞对抗异丙肾上腺素诱导的氧化应激及内质网应激反应[J].中国药理学通报,2011,27(3)：410-415.
[16]高玉琪,李志搡,吴宏超,等.心力衰竭患者肾上腺髓质素和前体N端20肽的改变[J].第一军医大学学报,2002,22(7)：632-634.
[17]Ojamaa K.Signaling mechanisms in thyroid hormone-induced cardiac hypertrophy. Vascul Pharmacol,2009,Decl 1.
[18]Wang K,Long B,Zhou J,et al.mRNA-9 and NFATc3 regulate myocardin in cardiac hypertrophy.J Biol Chem.2010 Apr 16;285(16):11903-12.
[19]RaizadeV,SkipperB,LuoW,et al.Intracardiac and intrarenal reninangiotensin systems: mechanisms of cardiovascular and renal effects,J Investig Med,2007, Nov;55(7):341-359.
[20]Alvarez-Guardia D,Palomer X,Coll T,et al.The p65 subunit of NF-{kappa}B binds to PGC-1{alpha},linking inflammation and metabolic disturbances in cardiac cells. Cardiovasc Res.2010 Mar 30.
[21]黄俊,覃国辉,马业新,等.转化生长因子-p1与大鼠心肌细胞肥大关系的实验研究[J].华中科技大学学报：医学版,2003,32(5)：484-486.
[22]KawanoS,KubotaT,MondenY,et al.Blockade of NF-kappaB improves cardiac function and survival after myocardial infarction[J].Am J Physiol Heart Circ Physiol,2006, 291(3):1337-1344.
[23]林谦,农一兵,黄启福.从心肌能量代谢探讨慢性心力衰竭心气虚证的实质,北京中医药大学学报,2007,7：51
[24]林谦通讯作者.从肌浆网钙转运变化探讨心肌肥厚气虚血瘀证实质,中国中医基础医学杂志,2009,15(5)：370-371.
[25]胡献国.补药之长-黄芪,人民军医出版社,2009,第1版.13-14.
[26]任澎,程祖亲,马依彤,等黄芪注射液对急性心力衰竭的血液动力学效应[J].中国中西医结合杂志,2004,24(3)：460
[27]张灼,陈立新,宋崇顺,等.黄芪多糖对大鼠心肌缺血一再灌注损伤后的保护作用[J].中国中医药信息、杂志,2007,14(2)：33-34.
[28]季宇彬,孙宇,江淼中药抗炎免疫有效成分药理与应用,人民卫生出版社2007,7,第1版,627-628.
[29]程航.美托洛尔联合复方丹参注射液治疗难治性心衰42例疗效观察,中国现代药物应用,2009,22(3)：133-134.
[30]沈映君,中药药理学专论,北京：人民卫生出版社,2009,7,第1版,204-205.
[31]Fildes JE,Shaw SM,Yonan N,et al.The immune system and chronic heart failure:is the heart in control? J AmColl Cardiol.2009,53:1013-1020.
[32]Moura LM,Rocha Gon calves F,ZamoranoJL,et al.New cardiovascular biomarkers: clinical implications in patients with valvular heart disease. Exprt Rev Ther Cardiovasc,2008, 6:945-954.
[33]Thanos D,Maniatis NF-kappa B:A lesson in family value[J].Cell,1995,80(4):529-532.
[34]Seko Y,Takahashi N,Yagita H,et al.Expression of eytokine mRNA in murine hearts with acute myocarditis caused by coxsackievirus B3[J].J Pathol,1997,183(1):105-108.
[35]Shakhov AN,Collart MA,Vassalli P,et al.KappaB type enhancers are involved in lipopolysaceharide mediated transcriptional activation of the tumor necrosis factor agene in primary macrophages[J].J Exp Med,1990,171(1):35-47.
[36]李科慧,刘唐威,伍伟峰,等.炎性细胞因子在慢性心力衰竭中的作用,医学综述,2007,5(13)：734-736.
[37]Parish RC,Evans D.Inflammation in chronic heart failureJl.Am Pharmacother,2008, 42(7):1002-161.
[38]Cesari M,Penninx BW,Newman AB.Inflamminaiory markers and onset of ABC study[J].cardiovasc Res,2003,108(19):2317-2322.
[39]LIM H,ZHU Y Z.Role of transforming growth factor-beta in the progression of heart failure[J].Cell Mol Life Sci,2006,63(22):2584-2596.
[40]Bloom BR,Bennett B,Oettgen HF,et al.Demonstration of delayed hypersensitivity to soluble antigens of chemically induced tumors by inhibition of macrophage migration.Proc Natl Acad Sci USA.1969Dec;64(4):1176-80.
[41]余丹青,陈纪言,周颖玲,等.冠状动脉粥样硬化与巨噬细胞移动抑制因子关系研究[J].岭南心血管病杂志,2003,9(2)：90-92.
[42]Zernecke A,Bernhagen J,Weber C.Macrophage inhibitory factor in cardiovascular disease[J].Circulation,2008,117(12):1594-1602.
[43]余文辉,周小梅,温文川,等.急性心肌梗死患者血浆巨噬细胞移动抑制因子水平变化的研究[J].中国免疫学杂志,2004,20(8)：575,577.
[44]刘媛,余细勇,林秋雄,等.充血性心力衰竭患者巨噬细胞移动抑制因子与心功能的相关性,第一军医大学学报,2003,23(11)：1169-70.
[45]Alvira CM,Abate A,Yangti,et al.Nuclear factor-KB activation in reonatal mouse lung protects against lipopoly saccharide-induced inflammation[J].Am J Respir Cirt Care Med,2007,175:805-815.
[46]Jones WK,BrownM,RenX,et al.NF-kappaB as an integrator of diverse signaling pathways:the heart of myocardial signaling?Cardiovasc Toxicol,2003;3(3):229-54.
[47]张子彬,Cheng TO,张玉传.充血性心力衰竭学.北京：科学技术文献出版社,2000：3-24.156-172,551-570.
[48]周金星,王建华主编.中药药理与临床研究进展(第4册).北京：军事医学科学出版社.1996：111-124
[49]张伯礼,复方丹参方的现代研究——组分配伍研制现代中药的理论与实践,人民军医出版社,2008,111,第1版,20
[50]许锦荣,陈玲,曾坚,等.老年心力衰竭患者核因子-κB与心功能的关系,实用医学杂志,2009,25(13),2080-2081.
[51]Hunt SA,Abraham WT,Chin MH,et al.ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult.Circulation,2005,Sep20; 112(12):154-235.
[52]李新民,吴红金,任建勋,等.参附复方对心肌梗死致心力衰竭大鼠脑尿钠的影响.中华中医药杂志,2011,8(26)：1859-1861.
[53]邓元江,梁伟雄,刘卫英,等.生脉胶囊对慢性心力衰竭大鼠心肌MMP-3与TIMP-1的影响,中华中医药杂志,2008,11(23)：1005-1008.
[54]Parish RC,Evans JD.Inflammation in chronic heart failure.Ann Pharmacother.2008 Jul;42(7):1002-16.Eurb2008May27.
[55]Meyer T,Stanske B,Kochen MM,et al.Elevated serum levels of interleukin-10 and tumor necrosis factor-α are both associated with vital exhaustion in patints with cardiovascular risk factors.Psychosomaties,2010,May;51(3):248-56.
[56]Wu CK,Lee JK,Chiang FT,et al.Plasma levels of tumor necrosis factor-a and interleukin6 are associated with diastolic heart failure through downregulation on of sarcoplasmic reticulum Ca2+-ATPase.Crit Care Med,2011,Jan 21.
[57]Guggilam A,Cardinale JP,Mariappan N,et al.Central TNF inhibition results in attenuatd neurohumoral excitation in heart failure:a role for superoxide and nitric oxide.Basic Res Cardiol,2011,Mar;106(2):273-86.Epub 2011 Jan 19.
[58]Matsummura T,Tsushima K,Ohtaki E,et al.Effects of carvedilol on plasma levels of interleukin-6 and tumor necrosis factor-alpha in nine patients with dilated cardiomyopathy[J]. J Cardiol,2002,May;39(5):253-7.
[59]Torre-Amione QAnkerSD,BourgeRC,et al.Results of a non-specific immunomodula-tion therapy in chronic heart failure(ACCLAIM trial):a placebo-controlled randomized trial. Lancet.2008,Jan 19,371(9608):228-36.
[60]HiguchiR,FocklerC,DollingerG,et al.Kinetic PCR analysis:real-time monitoring of DNA amplification reactions.Nature Biotchnology,1993,11:1026-1030.
[61]WongML,MedranoJF.Real-time PCR for mRNA quantitation[J].Biotechniques, 2005,39:75-85.
[62]中华医学会心血管病学分会,中华心血管病杂志编辑委员会,慢性心力衰竭诊断治疗指南,中华心血管病杂志,2007,12(35)：1076-1095.
[63]李建军.炎症学说与动脉粥样硬化,中国介入心脏病学大会,2011年特刊.
[64]王蕾,张世杰,王海鹏,等.阿托伐他汀对兔舒张性心力衰竭模型心室重构的影响.中国循环杂志,2010,25(3)：223-236.
[65]Sola S,Mir MQ,Lerakis S,et al.Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure[J].J Ant Coll Cardiol,2006,47(2):332-337.
[66]宗文纳,卢新政.2008年欧洲心力衰竭诊治指南解读,心血管病学进展,2009,1(30)：4-6.
[67]陈可冀,马晓娟,蒋跃绒,等.冠心病免疫相关基因组学的初步研究,中国分子心脏病学杂志,2007,5(7)：260-264.
[68]霍根红.心衰康对心肾阳虚型充血性心力衰竭免疫功能的影响,光明中医,2006,1(21)：44-46.
[69]杨志霞,李振彬,林谦,等.黄芪多糖联合丹参酮阻断慢性心衰大鼠NF-κB激活MIF、TNF-α及IL-6表达的效应,中华中医药杂志,2012年8月刊登
[2]Singh H,Sen R,Baltimore D,et al.A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes.Nature.1986 Jan9-15;319 (6049):154-8.
[3]Valen G,Yan ZQ,Hanson GK.Nuclear factor kappa-B and the heart[J].J Mol Cell Caridial,2001,38(2):307-314.
[4]曹雪涛.免疫学前沿进展,北京：人民卫生出版社,2009,3,第1版,637
[5]Siebenlist U,Franzoso G,Brown K.Structure regulation and function of NF-kappaB [J].Annu Rev Cell Biol,1994,10(2):405-455.
[6]杨敏烈.核因子-κB的作用及在心血管疾病治疗中的研究进展.南通大学学报(医学版),2008,28(1)：77-79.
[7]Vandermeeren M,et al.Dimethylfumarate is an inhibitor of cytokine induced E-selection,VCAM-1 and ICAM-1 expression in human endothelial cells[J].Biochem Biophys Res Commun,1997,234(1):19-23.
[8]Finco TS,Baldwin AS.Mechanistic aspects of NF-κB regulation:the emerging role of phosphorylation and proteolysis[J].Immunity,1995,3:263-272.
[9]Anlonella E,Janko W,Anna C,et al.The activation of the NF-κB system in chronic heart failure[J].J Am Coll Cardiol.2003,41:157-162.
[10]Anversa P,Nadal GB.Myocyte renewal and ventricular remodeling[J].Nature,2002, 415:240-243.
[11]Yndestad A,Damas JK,FieE,et al.Role of inflammation in the progression of heart failure[J].Curr Cardiol Rep,2007,3:236-241.
[12]Frantz S,Fraccarollo D,Wagner H,et al.Sustained activation of nuclear factor kappaB and activator protein-lin chronic heart failure,Cardiovasc Res,2003,57:749-756.
[13]Ogawa K,Hirooka Y,Kishi T,et al.Brain AT1 receptor activates the sympathetic nervous system through toll-like receptor-4 in mice with heart failure[J],J Cardiovasc Pharmacol,2011Nov;58(5):543-9.
[14]Siednienko J,Jankowska EA,Banasiak W,et al.Nuclear factor-kappaB activity in peripheral blood mononuclear cells in cachectic and non-cachectic patients with chronic heart failure.Int J Cardiol,2007,Nov15;122(2):111-6.Epub,2007,Jan30.
[15]LuzzaF,BruniF,RizzoF,et al Pathophysiology of congestive heart failure.Minerva Cardioangiol,2002,50:209-219.
[16]Deswal A,Petersen NJ,Feldman AM,et al. Cytokines and cytokine receptors in advanced heart failure:an analysis of the cytokine database from the Vesanrinone Trial(VEST)[J].Circulation,2001,103(11):2055-2059.
[17]Jones WK,Brown M,Ren X,et al.NF-kappa B as an integrator of diverse signaling pathways:the heart of myocardial signaling?Cardiovasc Toxicol,2003,3:229-254.
[18]Greenberg BJ,Treatment of heart failure state of the art and prospectives[J]. Cardiovasc Pharmacol,2001,38:59-63.
[19]Martinez RM.Cardiac remodeling and inflammation[J].Arch Cardiol Mex,2006,76: 58-66.
[20]戴闰柱.世纪之交的心力衰竭[J].中华心血管病杂志,2001,29(11)：641-3.
[21]ChandrashekharY.Role of apoptosis in ventricular remodeling[J].Curr Heart Fail Rep,2005,2(1):18-22.
[22]Toth MJ,Ades PA.Tischler MD,et al.Immune activation is associated with reducted skeletal muscle mass and physical function in chronic heart failure[J].Int J Cardiol,2005,14: 85-87.
[23]Frantz S,FraccarlloD,Wagner H,et al.Sustained activation of nuclear factor kappaB and activator protein-1 in chronic heart failure[J].Cardiovasc Rec,2003,57:749-756.
[24]Matsumori A,Anti-inflammatory therapy for heart failure[J].Current Opinion in Phamacology,2004,4:126.
[25]Li YY,Feng YG,Kadokami T,et al.Myocardial extracellure matrix remodeling in transgenic mice overexpressing tumor necrosis factor alpha can be modulated by anti-tumor necrosis factor alpha therapy[J].Proc Natl Acad Sci USA,2000,97(4):H12746-51.
[26]Spinale FG. Matrix metalloproteinases regulation and dysregulation in the falling heart[J].Circ Res,2002,90(2):520-530.
[27]朱茵,贾如意,高佩增.冠心病心力衰竭患者血清NF-KB水平变化及意义.山东医药,2010,50(23)：7-9.
[28]Ojamaa K.Signaling mechanisms in thyroid hormone-induced cardiac hypertrophy. Vascul Pharmacol.2009,Dec11.
[29]Alvarez-Guardia D,Palomer X,Coll T,et al.The p65 subunit of NF-{kappa)B binds to{alpha},linking inflammation and metabolic disturbances in cardiac cells, Cardiovasc Rs, 2010,Mar 30.
[30]Kumar S,Seqqat R.Chigurupati S,et al.Inhibition of nuclear factor-κB regresse cardiac hypertrophy by modulating the expression of extracellular matrix and adhesion molecules.Free Radic Biol,Med 2011 Jan 1:50(1):206-215.
[31]WongSC,Fukuchi M,Melnyk P,et al.Induction of cyclooxgenase-2 and activation of nuclear factor kappa B in myocardium of patints with congestive heart failure[J].Circulation, 1998,98(2):100-103.
[32]Cook SA,Novikoy MS,Ahn Y,et al.A20 is dynamically regulated in the heart and inhibitis the hypertrophic response[J].Circulation,2003,108:664-67.
[33]PurcellNH,Tang G,Mercuio F,et al.Activation of NF-κB is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes[J].Proc Natl Acad Sci USA,2001, 98:6668-6673.
[34]Gupta S,Purcell NH,Lin A,et al. Activation of nuclar factor-κB is necessary for myotrophin induced cardiac hypertrophy[J].J Cell Biol,2002,159:1019-28.
[35]Higuchi Y,Otsu K,Nishida K,et al.Involvement of reactive oxygen species mediated NF-κB activation in TNF-a induced cardiomyocyte hypertrophy[J].J Mol Cell Cardiol,2002, 34:233-240.
[36]Hirotani S,Otsu K,Nishida K,et al.Involvement of nuclear factor-KB and apoptosis signal regulating kinase-1 in Gprotein coupled receptor agonist induced cardiomyocyte hypertrophy [J].Circulation,2002,105,509-515.
[37]Fritzenwanger M,Foerster M,Meusel K,et al.Cardiotrophin-1 induces intercellular adhesion molecule-1 expression by nuclear factor kappa-B activation in human umbilical vein endothelial cells.Chin Med J(Engl).2008Dec,20;121(24):2592-8.
[38]Yuehua Li,Tuanzhu Ha. NF-κB activation is required for the development of cardie hypertrophy invivo[J].Am J Physiol Heart Circ Physiol,2004,287IH1712-20.
[39]De KeulenaerGW,Wang Y,Feng Y,et al.Identification of IEX-1 as a biomechanically controlled nuclear factor-κB target gene that inhibits cardiomyocyte hypertrophy[J].Circ Res,2002,90:690-696.
[40]Chen G,Zhou X,FloreaS,et al.Expression of active protein phosphatase-1,inhibitor-1 attenuates chronic beta-agonist-induced cardiac apoptosis.Basic Res Cardiol,2010,May 30.
[41]Monaco C,Paleolog E.Nuclear factor-κB:a potential therapeutic target in atheroscle-rosis and thrombosis[J].Cardiovasc Res,2004,61:671-682.
[42]Matsushita H,Morishita R,Nata T,et al.Hypoxia induced endothelial apoptosis through nuclear factor-kappaB mediated bcl suppression:in vivo evidence of the importance of NF-kappaB in endothelial cell regulation[J].Circ Res,2000,86(9):974-981.
[43]Matsumori A,Sasayama S.The role of inflammatory mediators in the failing heart: immunomodulation of cytokines in experimental models of heart failure[J].Heart Rev Fail, 2001,6(2):129-136.
[44]Chanani NK,Cowan DB,Takeuchi K,et al.Differential effects of amrinone and milrinone upon myocardial inflammatory signaling[J].Circulation,2002,106:1284-1289.
[45]Bhatt DL,Topol EJ.Need to test the arterial inflammation hypothesis[J].Circula-tion,2002,106:136-140.
[46]Ito H,Ono k,Nishio R,et al.Amiodarone inhibits interleukin-6 production and attenuates myocardial injury induced by viral myocarditis in mice[J].Cytokine hypertro-phy.2002,17:197-202.
[47]Mizuochi Y,Okajima K,Harada N,et al.Carvedilol,a nonselective beta-blocker, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro,Transl Res Apr,2007,Transl Apr;149(4):223-230.
[48]许锦荣,陈玲,曾坚,等.老年心力衰竭患者核因子-κB与心功能的关系,实用医学杂志,2009,25(13)：2080-2081.
[1]中华人民共和国卫生部药典委员会汇编.中华人民共和国药典(2005年版)一部[S].北京：化学工业出版社,2005,52-53.
[2]中华本草精选本/家中医药管理局《中华本草》编委会.—上海：上海科学技术出版社,1998,1(2009,5重印)：1653,1669.
[3]赵娜,郭治昕,赵雪,等.丹参的化学成分与药理作用[J].国外医药：植物药分册,2007,22(4)：155-160.
[4]叶勇.丹参有效成分分离的研究进展[J].药品评价,2005,2(2)：146-8,118
[5]中国医学科学院.中草药现代研究(第二册)[M].北京：北京医科大学、中国协和医科大学联合出版社,1996,50
[6]陈丽娜,朱晓新.丹参改善血液流变性的实验研究进展,中国中药杂志,2005,30(8)：630-633，640.
[7]蔡丽萍,习志刚,杨虹.丹参酮的药理作用和临床研究进展.广东药学院学报,2008,24(3)：321-4.
[8]王维婷,单成钢,倪大鹏,等.丹参有效成分代谢生理生化及分子生物学研究进展.中药材,2009,32(9)：1472-1476.
[9]梁雪丹,范田园,郑颖.以丹参素为指标成分的丹参制剂及其药动学研究概述.中国新药杂志,2008,17(21)：1838-1842.
[10]陈彦贾,晓斌,施亚芳,等.不同提取方法测定丹参药材中丹参素的含量的比较研究[J].江苏中医药,2003,24(6)：55-56.
[11]贾娜,项海芝,杨松松.丹参水溶性部分丹酚酸的进展述评.辽宁中医学院学报,2006,8(3)：41-42.
[12]张中堂,张群林,张云静,等.中药丹参有效成分的提取分离方法研究进展.时珍国医国药,2010,21(3)：728-730.
[13]龚丽娅,郑智,熊玮,等.丹参酮ⅡA抑制血管紧张素Ⅱ诱导的大鼠心肌细胞肥大[J].华西医学杂志,2004,19(1)：24-27.
[14]杨志霞,林谦,农一兵,等.黄芪多糖联合丹参酮对心衰大鼠心肌NF-κB通路过度激活的影响[J].北京中医药大学学报,2011,34(9)：609-612.
[15]范慧霞,药丹参药理作用研究概况[J].新疆中医药,2007,25(5)：113-6.
[16]Fu JJ, Huang H, Liu J,et al.TanshinoneⅡA protects cardiac myocytes against oxidative stress-triggered damage and apoptosis[J].Euro J Pharmacol,2007,568(1-3):213-221.
[17]YangR,LiuA,MaX,et al. Sodium tanshinone IIA sulfonate protects cardiomyocytes against oxidative stress-mediated apoptosis through inhibiting JNK activation[J]. J Cardiovasc Pharmacol,2008,51(4):396-401.
[18]Liu YL,Liu GT.Inhibition of human low-density lipoprotein by salviano licacid-A[J]. Atca Phar Sin,2002,37(2):81-85.
[19]吴立玲.缺血-再灌注损伤[M],//金惠铭,王建枝.病理生理学.第6版,北京：人民卫生出版社,2004,205
[20]朱立民,曾秋棠.丹参酮IIA磺酸钠对家兔在体外单相动作电位影响的研究[J].山东医药,2005,45(20)：22-23.
[21]梁文,曹西南.丹参在心脏保存中应用的研究进展,医学综述,2009,15(13)：2015-6.
[22]张洁,曾晓荣,杨艳,等.丹参酮HA磺酸钠和丹参素对猪冠状动脉平滑肌细胞钙激活钾通道的激活机制[J].中国药理学与毒理学杂志,2005,19(4)：270-273.
[23]邓惠英.丹参及其有效成份的药理研究概况.现代医药卫生,2007,23(12)：1812-3.
[24]刘光喜,黄韵诗.丹参对心血管作用的研究进展,中医药导报,2008,14(3)：86-88.
[25]高枫,孙桂波,聂媛媛,等.丹酚酸B对大鼠离体工作心脏血流动力学的影响,中国实验动物学报,2011,19(5)：396-399.
[26]郭伟强,曹婷婷,徐雯婧,等.丹参酮IIA对细胞因子IL6和IL-10的影响[J].技术,2008,18(6)：30-32.
[27]Miettinen KH,Lassus J,H arjola VP,et al.Prognosticrole of pro-and anti-inflammat-ory cytokines and the irpolym orphisms in acute decompensated heart failure[J].EurHeart Fail,2008,10(4):396-403.
[28]RoncoC.HaapioM,House AA,et al.Cardiorenal syndrome[J].Am Coll Cardiol,2008, 52(19):1527-1539.
[29]廖晓春,刘文举,扬海玉.丹参酮IIA磺酸钠对心肾综合征患者肾小球滤过率的影响[J].湖南中医药大学学报,2009,29(11)：23-24.
[30]Jang SI,Kim HJ,Kim YJ,et al.Tanshinone IIA inhibits LPS induced NF-κB activation in Raw 264.7 cells possible involvement of the NIK-IKK, EPK1/2,p38 and JNK pathways[J].Eur J Pharmacol,2006,542(1-3):1-7.
[31]齐艳艳,史永照.丹参对缺血再灌注损伤的保护作用及机制研究进展.上海中医药大学学报,2010,24(2)：89-91.
[32]陈树彤,史培杰,黄电波.复方丹参滴丸治疗冠心病合并高血脂症疗效观察[J].医学理论与实践,2007,2(7)：750-752.
[33]马海燕.低分子肝素联合丹参酮注射液治疗不稳定型心绞痛疗效观察,医学理论与实践,2010,23(12)：1455-1456.
[34]冯俊,张洁,郑智,等.丹参酮IIA抑制新生大鼠心肌细胞肥大的作用机制.中国急救医学,2006,26(14)：274-276.
[35]宋利,陶新为,钟晓辉.中药辅助治疗冠心病慢性心力衰竭41例.中国实用医 药,2009,4(24)：44-45.
[36]马晨,张善飞,曹彦光,等.丹参注射液对离体大鼠心肌能量代谢的调节作用.中国药科大学学报,2009,40(2)：147-151.
[37]Miodor.Generation of free radicals and/or active oxygen by light or irra diation of hydrogen peroxide or sodium hypochlorite[J].J Endod,2003,29(2):141-143.
[38]李湘平,尹桃.丹参多酚酸盐注射液治疗冠心病的疗效观察.中国现代医学杂志,2010,20(4)：619-621,624
[39]国家药典委员会.中华人民共和国药典临床用药须知中药卷[M].北京：人民卫生出版社,2005,331.
[40]刘孝蓉.复方丹参注射液联合酚妥拉明治疗肺心病心衰疗效观察.现代医药卫生,2010,26(19)：2906-2907.
[41]史载祥,汪燕,杜金行,等.丹参粉针联合西药治疗冠心病心绞痛临床观察.中国中医急症,2010,(6)：911-912.
[1]Hunt SA,Abraam WT,Chin MH,et al.ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult,Circulation,2005,112: 154-235.
[2]MartinezRM.Cardiac remodeling and inflammation[J].Arch CardiolMex,2006,76: S58-66.
[3]Katsuyamai L,Hirata Y,et al,derivative inhibits cytokine induced OS plessioii and NF-kappa B activation by preventing pho6phoryhtlon and degradation of kappaB-alpha OJJ Biochem(Tokyo),2001,129:585-591.
[4]Monsuez JJ,Escaut L,Teicher E,et al.Cytokines in HIV-associated cardiomyopathy, Int J Cardiol.2007 Aug 21; 120(2):150-157.
[5]Li Y,Ha T,Gao X,et al.NF-KB activation is required for the development of cardiac hypertrophy in vivo[J].Ant J Physiol Heart Circ Physiol,2004,287(4):H1712-1720.
[6]杨志霞,林谦,马利,等.黄芪多糖丹参酮对慢性心衰大鼠MIF表达的调控作用[J],中国药理学通报,2011,27(9)：1214-1217.
[7]杨志霞,林谦,农一兵,等.黄芪多糖联合丹参酮对心衰大鼠心肌NF-κB通路过度激活的影响[J].北京中医药大学学报,2011,34(9)：609-612.
[8]杨海波,李振民,阚秀莲,等.黄芪对慢性心力衰竭患者左室重构的影响[J].中西医结合心脑血管病杂志,2009,8(9)：1031-1032.
[9]谢鸣.中医方剂现代研究[M].北京：学苑出版社,1997：1034.
[10]朱嘉蓉,罗厚蔚.丹参酮Ⅱ的抑菌活性研究[J].中国药科大学学报,2004,35(4)：368
[1]Deten A,Holzl A,Leicht M,et al.Changes in extracellular matrix and in transforming growth factor beta isoforms after coronary artery ligation in rats[J].J Mol Cell Cardiol,2001, Jun;33(6):1191-1207.
[2]Gurgel CAS,Ramos EAG,Azevedo RA,et al.Expression of Ki-67,p53 and p63 proteins in keratocyst odontogenic tumours:an immunohistochemical study.J Mol Hist,2008,39:311-316.
[3]WongML,MedranoJF.Real-time PCR for mRNA quantitation[J].Biotechniques,2005, 39:75-85.
[1]李晓娜.益气活血法治疗心力衰竭近况,甘肃中医,2009,22(2)：16-17.
[2]傅向华,孙家安.心力衰竭的现代认识[J].床荟萃,2004,19(1)：55-58.
[3]解海宁,张艳,胡晓红,等.气虚血瘀水停在慢性心衰实质研究探讨.中华中医药学刊,2007,12(25)：2603-2604.
[4]严夏,李俊,方志坚,等.温阳活血法治疗慢性充血性心力衰竭的临床研究[J].上海中医药杂志,2005,39(8)：17-18.
[5]李小平.中药分期辩证治疗慢性充血性心力衰竭63例[J].陕西中医,2006,27(7)：775-776.
[6]戴霞.充血性心力衰竭的中医研究概况[J].北京中医,2005,24(1)：47
[7]周鲁,宋航.中药复方治疗充血性心力衰竭的用药分析[J].时珍国医国药,2005,16(3)：185-186.
[8]黄峻.心力衰竭治疗的现状和进展,岭南心血管病杂志,2010,16(2)：85-88.
[9]徐梦丹,戴秋燕.上海交通大学(医学版),2009,29(6)：649-653.
[10]张长军,于凤琴,徐淑玲,等.足月新生儿缺氧缺血性脑病与低钙血症[J].中国妇幼保健,2005,20(10)：1240-1241.
[11]吴晓光.细胞因子与心力衰竭关系的研究进展.中华保健医学杂志.2008,10(1)：72.
[12]Hirota H,Izumi M,Hamaguchi T,et al.Circulation interleukin-6 family cytokine and their receptors in patients with congestive heart failure [J].Heart Vssels,2004,19(5):237-241.
[13]傅广,赵水平.心力衰竭患者TNF-a和IL-6的变化及氯沙坦的影响[J].中国循环杂志,2005,16(4)：243-251.
[14]Gupfa S,Sen S.Role of the NF-kappaB signaling cascade and NF-kappaB targeted genes in failing human hearts.J MolMed,2005,83:993-1004.
[15]黄涌,阮经文,杨春涛,等.依达拉奉保护Hgc2心肌细胞对抗异丙肾上腺素诱导的氧化应激及内质网应激反应[J].中国药理学通报,2011,27(3)：410-415.
[16]高玉琪,李志搡,吴宏超,等.心力衰竭患者肾上腺髓质素和前体N端20肽的改变[J].第一军医大学学报,2002,22(7)：632-634.
[17]Ojamaa K.Signaling mechanisms in thyroid hormone-induced cardiac hypertrophy. Vascul Pharmacol,2009,Decl 1.
[18]Wang K,Long B,Zhou J,et al.mRNA-9 and NFATc3 regulate myocardin in cardiac hypertrophy.J Biol Chem.2010 Apr 16;285(16):11903-12.
[19]RaizadeV,SkipperB,LuoW,et al.Intracardiac and intrarenal reninangiotensin systems: mechanisms of cardiovascular and renal effects,J Investig Med,2007, Nov;55(7):341-359.
[20]Alvarez-Guardia D,Palomer X,Coll T,et al.The p65 subunit of NF-{kappa}B binds to PGC-1{alpha},linking inflammation and metabolic disturbances in cardiac cells. Cardiovasc Res.2010 Mar 30.
[21]黄俊,覃国辉,马业新,等.转化生长因子-p1与大鼠心肌细胞肥大关系的实验研究[J].华中科技大学学报：医学版,2003,32(5)：484-486.
[22]KawanoS,KubotaT,MondenY,et al.Blockade of NF-kappaB improves cardiac function and survival after myocardial infarction[J].Am J Physiol Heart Circ Physiol,2006, 291(3):1337-1344.
[23]林谦,农一兵,黄启福.从心肌能量代谢探讨慢性心力衰竭心气虚证的实质,北京中医药大学学报,2007,7：51
[24]林谦通讯作者.从肌浆网钙转运变化探讨心肌肥厚气虚血瘀证实质,中国中医基础医学杂志,2009,15(5)：370-371.
[25]胡献国.补药之长-黄芪,人民军医出版社,2009,第1版.13-14.
[26]任澎,程祖亲,马依彤,等黄芪注射液对急性心力衰竭的血液动力学效应[J].中国中西医结合杂志,2004,24(3)：460
[27]张灼,陈立新,宋崇顺,等.黄芪多糖对大鼠心肌缺血一再灌注损伤后的保护作用[J].中国中医药信息、杂志,2007,14(2)：33-34.
[28]季宇彬,孙宇,江淼中药抗炎免疫有效成分药理与应用,人民卫生出版社2007,7,第1版,627-628.
[29]程航.美托洛尔联合复方丹参注射液治疗难治性心衰42例疗效观察,中国现代药物应用,2009,22(3)：133-134.
[30]沈映君,中药药理学专论,北京：人民卫生出版社,2009,7,第1版,204-205.
[31]Fildes JE,Shaw SM,Yonan N,et al.The immune system and chronic heart failure:is the heart in control? J AmColl Cardiol.2009,53:1013-1020.
[32]Moura LM,Rocha Gon calves F,ZamoranoJL,et al.New cardiovascular biomarkers: clinical implications in patients with valvular heart disease. Exprt Rev Ther Cardiovasc,2008, 6:945-954.
[33]Thanos D,Maniatis NF-kappa B:A lesson in family value[J].Cell,1995,80(4):529-532.
[34]Seko Y,Takahashi N,Yagita H,et al.Expression of eytokine mRNA in murine hearts with acute myocarditis caused by coxsackievirus B3[J].J Pathol,1997,183(1):105-108.
[35]Shakhov AN,Collart MA,Vassalli P,et al.KappaB type enhancers are involved in lipopolysaceharide mediated transcriptional activation of the tumor necrosis factor agene in primary macrophages[J].J Exp Med,1990,171(1):35-47.
[36]李科慧,刘唐威,伍伟峰,等.炎性细胞因子在慢性心力衰竭中的作用,医学综述,2007,5(13)：734-736.
[37]Parish RC,Evans D.Inflammation in chronic heart failureJl.Am Pharmacother,2008, 42(7):1002-161.
[38]Cesari M,Penninx BW,Newman AB.Inflamminaiory markers and onset of ABC study[J].cardiovasc Res,2003,108(19):2317-2322.
[39]LIM H,ZHU Y Z.Role of transforming growth factor-beta in the progression of heart failure[J].Cell Mol Life Sci,2006,63(22):2584-2596.
[40]Bloom BR,Bennett B,Oettgen HF,et al.Demonstration of delayed hypersensitivity to soluble antigens of chemically induced tumors by inhibition of macrophage migration.Proc Natl Acad Sci USA.1969Dec;64(4):1176-80.
[41]余丹青,陈纪言,周颖玲,等.冠状动脉粥样硬化与巨噬细胞移动抑制因子关系研究[J].岭南心血管病杂志,2003,9(2)：90-92.
[42]Zernecke A,Bernhagen J,Weber C.Macrophage inhibitory factor in cardiovascular disease[J].Circulation,2008,117(12):1594-1602.
[43]余文辉,周小梅,温文川,等.急性心肌梗死患者血浆巨噬细胞移动抑制因子水平变化的研究[J].中国免疫学杂志,2004,20(8)：575,577.
[44]刘媛,余细勇,林秋雄,等.充血性心力衰竭患者巨噬细胞移动抑制因子与心功能的相关性,第一军医大学学报,2003,23(11)：1169-70.
[45]Alvira CM,Abate A,Yangti,et al.Nuclear factor-KB activation in reonatal mouse lung protects against lipopoly saccharide-induced inflammation[J].Am J Respir Cirt Care Med,2007,175:805-815.
[46]Jones WK,BrownM,RenX,et al.NF-kappaB as an integrator of diverse signaling pathways:the heart of myocardial signaling?Cardiovasc Toxicol,2003;3(3):229-54.
[47]张子彬,Cheng TO,张玉传.充血性心力衰竭学.北京：科学技术文献出版社,2000：3-24.156-172,551-570.
[48]周金星,王建华主编.中药药理与临床研究进展(第4册).北京：军事医学科学出版社.1996：111-124
[49]张伯礼,复方丹参方的现代研究——组分配伍研制现代中药的理论与实践,人民军医出版社,2008,111,第1版,20
[50]许锦荣,陈玲,曾坚,等.老年心力衰竭患者核因子-κB与心功能的关系,实用医学杂志,2009,25(13),2080-2081.
[51]Hunt SA,Abraham WT,Chin MH,et al.ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult.Circulation,2005,Sep20; 112(12):154-235.
[52]李新民,吴红金,任建勋,等.参附复方对心肌梗死致心力衰竭大鼠脑尿钠的影响.中华中医药杂志,2011,8(26)：1859-1861.
[53]邓元江,梁伟雄,刘卫英,等.生脉胶囊对慢性心力衰竭大鼠心肌MMP-3与TIMP-1的影响,中华中医药杂志,2008,11(23)：1005-1008.
[54]Parish RC,Evans JD.Inflammation in chronic heart failure.Ann Pharmacother.2008 Jul;42(7):1002-16.Eurb2008May27.
[55]Meyer T,Stanske B,Kochen MM,et al.Elevated serum levels of interleukin-10 and tumor necrosis factor-α are both associated with vital exhaustion in patints with cardiovascular risk factors.Psychosomaties,2010,May;51(3):248-56.
[56]Wu CK,Lee JK,Chiang FT,et al.Plasma levels of tumor necrosis factor-a and interleukin6 are associated with diastolic heart failure through downregulation on of sarcoplasmic reticulum Ca2+-ATPase.Crit Care Med,2011,Jan 21.
[57]Guggilam A,Cardinale JP,Mariappan N,et al.Central TNF inhibition results in attenuatd neurohumoral excitation in heart failure:a role for superoxide and nitric oxide.Basic Res Cardiol,2011,Mar;106(2):273-86.Epub 2011 Jan 19.
[58]Matsummura T,Tsushima K,Ohtaki E,et al.Effects of carvedilol on plasma levels of interleukin-6 and tumor necrosis factor-alpha in nine patients with dilated cardiomyopathy[J]. J Cardiol,2002,May;39(5):253-7.
[59]Torre-Amione QAnkerSD,BourgeRC,et al.Results of a non-specific immunomodula-tion therapy in chronic heart failure(ACCLAIM trial):a placebo-controlled randomized trial. Lancet.2008,Jan 19,371(9608):228-36.
[60]HiguchiR,FocklerC,DollingerG,et al.Kinetic PCR analysis:real-time monitoring of DNA amplification reactions.Nature Biotchnology,1993,11:1026-1030.
[61]WongML,MedranoJF.Real-time PCR for mRNA quantitation[J].Biotechniques, 2005,39:75-85.
[62]中华医学会心血管病学分会,中华心血管病杂志编辑委员会,慢性心力衰竭诊断治疗指南,中华心血管病杂志,2007,12(35)：1076-1095.
[63]李建军.炎症学说与动脉粥样硬化,中国介入心脏病学大会,2011年特刊.
[64]王蕾,张世杰,王海鹏,等.阿托伐他汀对兔舒张性心力衰竭模型心室重构的影响.中国循环杂志,2010,25(3)：223-236.
[65]Sola S,Mir MQ,Lerakis S,et al.Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure[J].J Ant Coll Cardiol,2006,47(2):332-337.
[66]宗文纳,卢新政.2008年欧洲心力衰竭诊治指南解读,心血管病学进展,2009,1(30)：4-6.
[67]陈可冀,马晓娟,蒋跃绒,等.冠心病免疫相关基因组学的初步研究,中国分子心脏病学杂志,2007,5(7)：260-264.
[68]霍根红.心衰康对心肾阳虚型充血性心力衰竭免疫功能的影响,光明中医,2006,1(21)：44-46.
[69]杨志霞,李振彬,林谦,等.黄芪多糖联合丹参酮阻断慢性心衰大鼠NF-κB激活MIF、TNF-α及IL-6表达的效应,中华中医药杂志,2012年8月刊登