中药单体对cTnT~（R141W）转基因扩张型心肌病小鼠模型的治疗作用及机理研究
|
摘要
第一部分人参皂甙Rb1对cTnTR141W转基因扩张型心肌病小鼠模型的治疗作用及机理研究
背景近年来心血管领域的一个研究热点是心血管重构的药物干预。已发现多种西药及中药有效成分,能够逆转高血压、心梗等导致的心脏重构,尤其是左心室肥大(left ventricular hypertrophy, LVH)的发生和发展。然而却缺乏能够有效逆转扩张型心肌病(dilated cardiomyopathy, DCM)的心脏扩张及心功能衰竭的药物。本文从对心血管疾病有较好疗效的中药单体中挑选出11种,利用本所遗传中心建立的cTnTR141W转基因DCM小鼠模型,筛选得到可改善DCM心脏功能及重构的药物两种,分别是Rb1(Ginsenoside-Rb1)和TMPP (Tetramethylpyrazine phosphate),我们从多个层次研究其药理作用并进行机制的研究。方法对2月龄的cTnTR141W阳性鼠进行心脏超声检测,计算左心室收缩期内径(leftventricular internal diameter at end-systole, LVIDs)的平均值和95%的可信区间。我们将95%的可信区间的上限作为心脏扩张的标准,排除部分表型不显著的cTnTR141W阳性鼠。其余的阳性鼠被随机分为模型组和人参皂甙Rb1治疗组(70 mg／kg／d)。用相同年龄的阴性鼠作为对照组。分组后每个月进行一次超声。连续给药7个月。在长期给药的过程中以及给药终点,观察各给药组与模型组心功能各项指标的变化。进行Kaplan-Meier生存分析。计算心重指数。HE染色和Masson染色观察心肌细胞变化及间质变化。透射电镜分析心肌超微结构。RT-PCR检测心肌粘附蛋白Cx40、Cx43、E-cad、N-cad、P-cad、itga8和itgb1bp3的表达。免疫荧光激光共聚焦观察心肌粘附分子Itga8的表达与分布。Western blot检测心脏HB-EGF, pSTAT3, STAT3表达水平。结果Rb1长期给药能显著改善该模型的心功能和心脏几何构型,将死亡率降低50%。Rb1治疗组心重指数降低11.3%(P<0.05)。光镜观察显示Rb1能减轻心肌细胞排列紊乱以及间质纤维化。透射电镜观察显示Rb1能减轻心肌超微结构的破坏。RT-PCR结果显示,在模型中Cx40表达降低,E-cad、itga8和itgb1bp3表达升高,但在Rb1组中接近正常水平。免疫荧光激光共聚焦结果显示Rb1可降低Itga8的表达量并调节其分布。Western blot结果显示Rb1能够显著降低模型中的HB-EGF及pSTAT3的表达,但tSTAT3的表达在三组无显著差异。结论本研究显示,Rb1与TMPP可作为治疗遗传性DCM的候选药物。Rb1可改善扩张型心肌病模型的心功能,抑制心脏重构,其作用可能部分通过调节粘附蛋白的表达,抑制心肌病发生中的HB-EGF表达及抑制下游信号pSTAT3的激活实现的。
第二部分磷酸川芎嗪对cTnTR141W转基因扩张型心肌病小鼠模型的治疗作用及机理研究
目的利用cTnTR141W转基因扩张型心肌病小鼠模型,研究磷酸川芎嗪(TMPP)对遗传性扩张型心肌病心功能及重构的影响,并对其机制进行研究。
方法将cTnTR141W转基因阳性鼠随机分为模型组和TMPP组(45mg／kg／d),连续给药7个月,取同龄阴性鼠作为对照组。超声检测心脏功能及几何构型。用Kaplan-Meier法进行生存分析。计算心重指数。RT-PCR检测心肌肥厚标志基因的表达。HE染色和Masson染色观察心肌细胞变化及间质变化。透射电镜分析心肌超微结构。Western blot和免疫荧光激光共聚焦观察心肌肌小节蛋白Myotilin和MLC2的表达与分布。RT-PCR检测心肌钙相关信号CaM/CaMKⅡ通路的表达情况。
结果TMPP长期给药能显著改善该模型的心功能和构型,将死亡率降低54%。TMPP显著降低心重指数(P<0.05),并降低心肌肥大标志基因ACTA1、BNP的表达,即减轻了扩心病小鼠的心肌肥厚。光镜观察显示TMPP能减轻心肌细胞排列紊乱以及间质纤维化。透射电镜观察显示Rbl能减轻心肌超微结构的破坏。Western blot及免疫荧光激光共聚焦结果显示,在模型组中,心肌肌小节Z-disc蛋白Myotilin表达升高,收缩蛋白MLC2磷酸化程度降低,给药处理后其表达接近正常水平。RT-PCR结果显示,在模型组中,心肌钙信号通路CaM/CaMKⅡ被激活,TMPP对该信号通路有抑制作用。
结论TMPP可改善扩张型心肌病模型的心功能,抑制心脏重构,其作用可能部分通过抑制钙激活信号通路包括CaM/CaMKⅡ通路而实现的。
第三部分心脏特异表达NOL3转基因小鼠的建立
目的建立心脏特异表达NOL3转基因小鼠,用于研究该基因在心肌病发病中的作用。
方法Western blot检测小鼠NOL3表达谱。构建αMHC-NOL3表达载体,显微注射法建立NOL3转基因小鼠。PCR鉴定转基因鼠的基因型,心脏超声检测转基因及野生型小鼠心脏功能及几何构型。
结果NOL3在1月龄野生型鼠心脏、脑、骨骼肌中的高表达,在心脏中的表达不随年龄而改变。通过转基因小鼠的筛选,得到了3个NOL3转基因品系,其中1个品系心脏NOL3蛋白表达量与野生型鼠相比明显增加。单转NOL3基因的小鼠心脏功能及几何构型与野生型小鼠相比无显著变化。
结论成功建立了心脏特异表达NOL3转基因小鼠,为进一步和心肌病小鼠模型杂交,研究该基因在心肌病发病中的作用提供了工具。
The effects and mechanisms of ginsenoside-Rbl on DCM in the cTnTK141W transgenic mouse
Backgroud The researches of inhibition of cardiac remodeling by drugs have been developed rapidly in recent years. It has been found that many effective components in Chinese herb could prevent the development of cardiac remodeling especially left ventricular hypertrophy, which occurred in hypertension, myocardial infarcion. But the study about the medicinal therapy for DCM was absent. Here, using the cTnTR141W transgenic mouse model of DCM, tetramethylpyrazine phosphate (TMPP) or ginsenoside-Rb1 were screening out from 11 kinds of compounds from Chinese herbs which showed beneficial effect on cardiovascular diseases, as the potential drugs for prevention of cardiac dysfunction and dilation in DCM. We further studied the effects and the possible underlying mechanisms of Rbl on cardiac remodeling of dilated cardiomyopathy in cTnTR141W transgenic mouse.
Methods We performed M-mode echocardiography in aMHC-cTnTR141W transgenic mice at the ages of 2 months, which is considered the predilated stage of DCM. We determined the mean and the 95%confidence interval (CI) of the left ventricular internal diameter at end-systole (LVIDs) in the transgenic mice. We used the upper limit of the 95%CI as the evidence for cardiac dilation and excluded the cTnTR141W mice with no significantly phenotype of DCM. The remainder transgenic mice were randomized to model group or drug group (Rb1,70 mg/Kg/d). Age-matched nontransgenic mice drinking water were used as wild type control. The drug was administered for 7 months. We detected the cardiac function and geometry by echocardiography once 1 month. Histology and transmission electron microscopy were used to assess myocardial organization, myocardial interstitial fibrosis and ultrastructure. The expression of adhesion proteins was detected by RT-PCR. Immunofluorescence was performed to examine localization of Itga8. The expression of HB-EGF, pSTAT3 and STAT3 were detected by western blot.
Results We found that long-term administration of ginsenoside-Rb1 significantly improved cardiac function and reduced mortality by 50%. The HW/BW ratio of Rbl-treated mice was significantly lower than that of placebo mice (11.3%, P< 0.05). Histological analysis showed that Rb1 attenuated the myocardial disarray, decreased the interstitial fibrosis, and ultrastructural abnormality in the cTnTR141W heart. RT-PCR revealed that the expression of Cx40, E-cad, itga8 and itgb 1 bp3 were turned over to nearly normal levels in the Rb1 group, while the decreased expression of Cx40 and the increased expression of E-cad, itga8 and itgb 1 bp3 were detected in the placebo group. Confocal immunofluorescence showed that Rb1 regulated the distribution of Itga8. Western blot analysis indicated that Rb1 treatment significantly downregulated HB-EGF and pSTAT3 expression, which were steadily overexpressed in the placebo mice.
Conclusion We showed that Rb1 and TMPP could be the potential drugs for DCM therapy. These findings revealed that Rb1 could improve cardiac function and inhibit cardiac remodeling of DCM in cTnTR141W transgenic mice, partly through regulating adhesion proteins expression and downregulated the HB-EGF expression and STAT3 activation during development of dilated cardiomyopathy in the cTnTR141W transgenic mice. The effects and mechanisms of tetramethvlpvrazine phosphate on DCM in the cTnTR141w transgenic mouse
Background and purpose:Dilated cardiomyopathy (DCM) is the most common cause of heart failure. Familial DCM (FDCM) may account for 20-48%of DCM, and specific medicines for its treatment are not currently available. Tetramethylpyrazine (TMP) has been shown to provide a substantial cardioprotective effect. In the present study, we used the cTnTR141W transgenic mouse model to test the effect of tetramethylpyrazine phosphate (TMPP) on FDCM.
Experimental approach:We evaluated the effect of TMPP on cardiac function and geometry by M-mode echocardiography once a month after randomization. The cardiac hypertrophic markers were analyzed, the microstructure and ultrastructure of heart were observed, and the expression and localization of structural proteins were detected in the mice aged 6 months. In addition, CaM/CaMK II signaling pathway was investigated as the possible intracellular mechanism.
Key results:TMPP significantly improved cardiac function and decreased mortality of cTnTR141W mice by 54% after 7 months of treatment. The HW/BW ratio, and gene expression of hypertrophic markers (NPPB, ACTA1) in cTnTR141W mice was decreased remarkedly by TMPP treatment. Histologic analysis showed that TMPP reduced myocyte disarray, interstitial fibrosis and ultrastructural abnormality in cTnTR141W mice. Western blot and immunofluorescence analysis indicated that TMPP decreased the expression of sarcomeric protein myotilin while increasing the expression of MLC2 in cTnTR141w mice. RT-PCR revealed an inhibition effect of TMPP on CaM/CaMKⅡsignaling pathway.
Conclusions and implications:TMPP was shown to prevent heart failure and left ventricular remodeling in the cTnTR141W transgenic mouse of DCM, and it mechanism may be related to its inhibition of CaM/CaMK II signaling pathway.
Abbreviations:DCM, dilated cardiomyopathy; FDCM, familial DCM; cTnT, cardiac troponin T; TMPP, Tetramethylpyrazine phosphate; HW/BW, heart weight/body weight; The establishment of heart specific NOL3 gene transgenic mice
Objective To establish nucleolar protein 3 (NOL3) transgenic mice and investigate its effect on the development of cardiomyopathy.
Methods The NOL3 expression in the different tissues and different ages of mice was detected with western blot. Transgenic mice were generated by the method of microinjection. The genotype of transgenic lines was identified by PCR. The cardiac function and geometry were detected by echocardiography.
Results The western blot analysis showed that NOL3 was expressed in quite higher levels in the tissues of heart, muscle and brain than in other tissues. The NOL3 expression in the heart maintained a high level from newborn to adult. Three founders of hearts specific a-MHC-NOL3 transgenic mice were established and one high-level expression line was identified. The transgenic gene itself did not affect the cardiac function and geometry compared with the wild type mice.
Conclusion The transgenic mice with cardiac-specific expression of the human NOL3 gene were established successfully and it can be used to cross with the DCM and HCM models to investigate the function of NOL3 gene on the development of cardiomyopathy.
背景近年来心血管领域的一个研究热点是心血管重构的药物干预。已发现多种西药及中药有效成分,能够逆转高血压、心梗等导致的心脏重构,尤其是左心室肥大(left ventricular hypertrophy, LVH)的发生和发展。然而却缺乏能够有效逆转扩张型心肌病(dilated cardiomyopathy, DCM)的心脏扩张及心功能衰竭的药物。本文从对心血管疾病有较好疗效的中药单体中挑选出11种,利用本所遗传中心建立的cTnTR141W转基因DCM小鼠模型,筛选得到可改善DCM心脏功能及重构的药物两种,分别是Rb1(Ginsenoside-Rb1)和TMPP (Tetramethylpyrazine phosphate),我们从多个层次研究其药理作用并进行机制的研究。方法对2月龄的cTnTR141W阳性鼠进行心脏超声检测,计算左心室收缩期内径(leftventricular internal diameter at end-systole, LVIDs)的平均值和95%的可信区间。我们将95%的可信区间的上限作为心脏扩张的标准,排除部分表型不显著的cTnTR141W阳性鼠。其余的阳性鼠被随机分为模型组和人参皂甙Rb1治疗组(70 mg／kg／d)。用相同年龄的阴性鼠作为对照组。分组后每个月进行一次超声。连续给药7个月。在长期给药的过程中以及给药终点,观察各给药组与模型组心功能各项指标的变化。进行Kaplan-Meier生存分析。计算心重指数。HE染色和Masson染色观察心肌细胞变化及间质变化。透射电镜分析心肌超微结构。RT-PCR检测心肌粘附蛋白Cx40、Cx43、E-cad、N-cad、P-cad、itga8和itgb1bp3的表达。免疫荧光激光共聚焦观察心肌粘附分子Itga8的表达与分布。Western blot检测心脏HB-EGF, pSTAT3, STAT3表达水平。结果Rb1长期给药能显著改善该模型的心功能和心脏几何构型,将死亡率降低50%。Rb1治疗组心重指数降低11.3%(P<0.05)。光镜观察显示Rb1能减轻心肌细胞排列紊乱以及间质纤维化。透射电镜观察显示Rb1能减轻心肌超微结构的破坏。RT-PCR结果显示,在模型中Cx40表达降低,E-cad、itga8和itgb1bp3表达升高,但在Rb1组中接近正常水平。免疫荧光激光共聚焦结果显示Rb1可降低Itga8的表达量并调节其分布。Western blot结果显示Rb1能够显著降低模型中的HB-EGF及pSTAT3的表达,但tSTAT3的表达在三组无显著差异。结论本研究显示,Rb1与TMPP可作为治疗遗传性DCM的候选药物。Rb1可改善扩张型心肌病模型的心功能,抑制心脏重构,其作用可能部分通过调节粘附蛋白的表达,抑制心肌病发生中的HB-EGF表达及抑制下游信号pSTAT3的激活实现的。
第二部分磷酸川芎嗪对cTnTR141W转基因扩张型心肌病小鼠模型的治疗作用及机理研究
目的利用cTnTR141W转基因扩张型心肌病小鼠模型,研究磷酸川芎嗪(TMPP)对遗传性扩张型心肌病心功能及重构的影响,并对其机制进行研究。
方法将cTnTR141W转基因阳性鼠随机分为模型组和TMPP组(45mg／kg／d),连续给药7个月,取同龄阴性鼠作为对照组。超声检测心脏功能及几何构型。用Kaplan-Meier法进行生存分析。计算心重指数。RT-PCR检测心肌肥厚标志基因的表达。HE染色和Masson染色观察心肌细胞变化及间质变化。透射电镜分析心肌超微结构。Western blot和免疫荧光激光共聚焦观察心肌肌小节蛋白Myotilin和MLC2的表达与分布。RT-PCR检测心肌钙相关信号CaM/CaMKⅡ通路的表达情况。
结果TMPP长期给药能显著改善该模型的心功能和构型,将死亡率降低54%。TMPP显著降低心重指数(P<0.05),并降低心肌肥大标志基因ACTA1、BNP的表达,即减轻了扩心病小鼠的心肌肥厚。光镜观察显示TMPP能减轻心肌细胞排列紊乱以及间质纤维化。透射电镜观察显示Rbl能减轻心肌超微结构的破坏。Western blot及免疫荧光激光共聚焦结果显示,在模型组中,心肌肌小节Z-disc蛋白Myotilin表达升高,收缩蛋白MLC2磷酸化程度降低,给药处理后其表达接近正常水平。RT-PCR结果显示,在模型组中,心肌钙信号通路CaM/CaMKⅡ被激活,TMPP对该信号通路有抑制作用。
结论TMPP可改善扩张型心肌病模型的心功能,抑制心脏重构,其作用可能部分通过抑制钙激活信号通路包括CaM/CaMKⅡ通路而实现的。
第三部分心脏特异表达NOL3转基因小鼠的建立
目的建立心脏特异表达NOL3转基因小鼠,用于研究该基因在心肌病发病中的作用。
方法Western blot检测小鼠NOL3表达谱。构建αMHC-NOL3表达载体,显微注射法建立NOL3转基因小鼠。PCR鉴定转基因鼠的基因型,心脏超声检测转基因及野生型小鼠心脏功能及几何构型。
结果NOL3在1月龄野生型鼠心脏、脑、骨骼肌中的高表达,在心脏中的表达不随年龄而改变。通过转基因小鼠的筛选,得到了3个NOL3转基因品系,其中1个品系心脏NOL3蛋白表达量与野生型鼠相比明显增加。单转NOL3基因的小鼠心脏功能及几何构型与野生型小鼠相比无显著变化。
结论成功建立了心脏特异表达NOL3转基因小鼠,为进一步和心肌病小鼠模型杂交,研究该基因在心肌病发病中的作用提供了工具。
The effects and mechanisms of ginsenoside-Rbl on DCM in the cTnTK141W transgenic mouse
Backgroud The researches of inhibition of cardiac remodeling by drugs have been developed rapidly in recent years. It has been found that many effective components in Chinese herb could prevent the development of cardiac remodeling especially left ventricular hypertrophy, which occurred in hypertension, myocardial infarcion. But the study about the medicinal therapy for DCM was absent. Here, using the cTnTR141W transgenic mouse model of DCM, tetramethylpyrazine phosphate (TMPP) or ginsenoside-Rb1 were screening out from 11 kinds of compounds from Chinese herbs which showed beneficial effect on cardiovascular diseases, as the potential drugs for prevention of cardiac dysfunction and dilation in DCM. We further studied the effects and the possible underlying mechanisms of Rbl on cardiac remodeling of dilated cardiomyopathy in cTnTR141W transgenic mouse.
Methods We performed M-mode echocardiography in aMHC-cTnTR141W transgenic mice at the ages of 2 months, which is considered the predilated stage of DCM. We determined the mean and the 95%confidence interval (CI) of the left ventricular internal diameter at end-systole (LVIDs) in the transgenic mice. We used the upper limit of the 95%CI as the evidence for cardiac dilation and excluded the cTnTR141W mice with no significantly phenotype of DCM. The remainder transgenic mice were randomized to model group or drug group (Rb1,70 mg/Kg/d). Age-matched nontransgenic mice drinking water were used as wild type control. The drug was administered for 7 months. We detected the cardiac function and geometry by echocardiography once 1 month. Histology and transmission electron microscopy were used to assess myocardial organization, myocardial interstitial fibrosis and ultrastructure. The expression of adhesion proteins was detected by RT-PCR. Immunofluorescence was performed to examine localization of Itga8. The expression of HB-EGF, pSTAT3 and STAT3 were detected by western blot.
Results We found that long-term administration of ginsenoside-Rb1 significantly improved cardiac function and reduced mortality by 50%. The HW/BW ratio of Rbl-treated mice was significantly lower than that of placebo mice (11.3%, P< 0.05). Histological analysis showed that Rb1 attenuated the myocardial disarray, decreased the interstitial fibrosis, and ultrastructural abnormality in the cTnTR141W heart. RT-PCR revealed that the expression of Cx40, E-cad, itga8 and itgb 1 bp3 were turned over to nearly normal levels in the Rb1 group, while the decreased expression of Cx40 and the increased expression of E-cad, itga8 and itgb 1 bp3 were detected in the placebo group. Confocal immunofluorescence showed that Rb1 regulated the distribution of Itga8. Western blot analysis indicated that Rb1 treatment significantly downregulated HB-EGF and pSTAT3 expression, which were steadily overexpressed in the placebo mice.
Conclusion We showed that Rb1 and TMPP could be the potential drugs for DCM therapy. These findings revealed that Rb1 could improve cardiac function and inhibit cardiac remodeling of DCM in cTnTR141W transgenic mice, partly through regulating adhesion proteins expression and downregulated the HB-EGF expression and STAT3 activation during development of dilated cardiomyopathy in the cTnTR141W transgenic mice. The effects and mechanisms of tetramethvlpvrazine phosphate on DCM in the cTnTR141w transgenic mouse
Background and purpose:Dilated cardiomyopathy (DCM) is the most common cause of heart failure. Familial DCM (FDCM) may account for 20-48%of DCM, and specific medicines for its treatment are not currently available. Tetramethylpyrazine (TMP) has been shown to provide a substantial cardioprotective effect. In the present study, we used the cTnTR141W transgenic mouse model to test the effect of tetramethylpyrazine phosphate (TMPP) on FDCM.
Experimental approach:We evaluated the effect of TMPP on cardiac function and geometry by M-mode echocardiography once a month after randomization. The cardiac hypertrophic markers were analyzed, the microstructure and ultrastructure of heart were observed, and the expression and localization of structural proteins were detected in the mice aged 6 months. In addition, CaM/CaMK II signaling pathway was investigated as the possible intracellular mechanism.
Key results:TMPP significantly improved cardiac function and decreased mortality of cTnTR141W mice by 54% after 7 months of treatment. The HW/BW ratio, and gene expression of hypertrophic markers (NPPB, ACTA1) in cTnTR141W mice was decreased remarkedly by TMPP treatment. Histologic analysis showed that TMPP reduced myocyte disarray, interstitial fibrosis and ultrastructural abnormality in cTnTR141W mice. Western blot and immunofluorescence analysis indicated that TMPP decreased the expression of sarcomeric protein myotilin while increasing the expression of MLC2 in cTnTR141w mice. RT-PCR revealed an inhibition effect of TMPP on CaM/CaMKⅡsignaling pathway.
Conclusions and implications:TMPP was shown to prevent heart failure and left ventricular remodeling in the cTnTR141W transgenic mouse of DCM, and it mechanism may be related to its inhibition of CaM/CaMK II signaling pathway.
Abbreviations:DCM, dilated cardiomyopathy; FDCM, familial DCM; cTnT, cardiac troponin T; TMPP, Tetramethylpyrazine phosphate; HW/BW, heart weight/body weight; The establishment of heart specific NOL3 gene transgenic mice
Objective To establish nucleolar protein 3 (NOL3) transgenic mice and investigate its effect on the development of cardiomyopathy.
Methods The NOL3 expression in the different tissues and different ages of mice was detected with western blot. Transgenic mice were generated by the method of microinjection. The genotype of transgenic lines was identified by PCR. The cardiac function and geometry were detected by echocardiography.
Results The western blot analysis showed that NOL3 was expressed in quite higher levels in the tissues of heart, muscle and brain than in other tissues. The NOL3 expression in the heart maintained a high level from newborn to adult. Three founders of hearts specific a-MHC-NOL3 transgenic mice were established and one high-level expression line was identified. The transgenic gene itself did not affect the cardiac function and geometry compared with the wild type mice.
Conclusion The transgenic mice with cardiac-specific expression of the human NOL3 gene were established successfully and it can be used to cross with the DCM and HCM models to investigate the function of NOL3 gene on the development of cardiomyopathy.
引文
[1]Richardson P, Mckenna W, Bristow M, et al. Report of the 1995 world health organization/international society and federation of cardiolgy task force on the definition and classification of cardiomyopathies [J]. Circulation,1996,93:841-842.
[2]Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies [J]. Circulation,2006,113:1807-1816.
[3]Ho KK, Anderson KM, Kannel WB, et al. Survival after the onset of congestive heart failure in Framingham heart study subjects [J]. Circulation,1993,88:107-115.
[4]Takahashi M, Takeda S, Kurokawa S, et al. Cyclic GMP production by ANP, BNP, and NO during worsening and improvement of chronic heart failure [J]. Jpn Heart, 2003,44(5):713-24.
[5]Vogt AM, Kubler W. Heart failure:is there an energy deficit contributing to contractile dysfunction [J]. Basic Res Cardiol,1998,93(1):1-10.
[6]Beckemeier ME, Bora PS. Fatty acid ethyl esters:potentially toxic products of myocardial ethanol metabolism [J]. Mol Cell Cardiol,1998,30(11):2487-94.
[7]Ikeda Y, Yamada M, Matsuzaki M,et al. Multicenter clinical trial of angiotensin receptor blocker in patients with chronic heart failure:review of recent clinical trial [J]. Nippon Rinsho,2002,60(10):2028-33.
[8]Umemoto S, Kawahara S, Hashimoto R, et al.Angiotensin receptor blockers in chronic heart failure [J]. Nippon Rinsho,2003,61(9):1683-9.
[9]白洁,张国辉.醛固酮受体拮抗剂在扩张型心肌病中的应用.心血管病学进展,2006,27(6)：
[10]Bevilacqua M, Salio M, Cardano P, et al. Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure:the Valsartan Heart Failure Trial (Val-HeFT) [J]. Circulation,2002,106(19):2454-8.
[11]Klein L, O'Connor CM, Gattis WA, et al. Pharmacologic therapy for patients with chronic heart failure and reduced systolic function:review of trials and practical considerations [J]. Am J Cardiol,2003,91(9A):18F-40F.
[12]Elkayam U. Calcium channel blockers in heart failure [J]. Cardiology,1998,89(suppl 1):38-46.
[13]Figulla HR. Gietzen F, Zeymer U, et al. Diltiazem improves cardiac func-tion and exercise capacity in patients with idiopathic dilated cardiomyopa-thy.results of the diltiazem in dilated cardiomyopathy trial [J]. Circulation,1996,94:346-352.
[14]Packer M, O'connor CM, Ghali JK, et al. Effect of amoldipine on morgidity and mortality in severe chronic heart failure.prospective randomized amlodipine survival evaluation study group [J]. N Engl J Med,1996,335:1107-1114.
[15]Zhang X, Hintze TH. Amlodipine releases nitric oxide from canine coronary microvessels:an unexpected mechanism of action of a calcium channel-blocking agent [J]. Circulation,1998,97:576-580.
[16]Mohler ER, Sorensen LC, Fhali JK, et al. Role of cytokines in the mechanism of acton of amlodipine:the praise heart failure trial [J]. J Am Coll Cardiol,1997,30: 34-41.
[17]Constant J. A review of why and how we may use β-blockers in congestive heart failure [J]. Chest,1998,113:800-808.
[18]Waagstein F, Bristow MR, Swedberg K, et al. Beneficial effect of metoprolol in idiopathic dilated cardiomypathy [J]. Lancet,1993,342:1441-1446.
[19]Talwar KK, Bhrargava B, Upasani PT, et al. Hemodynamic predictors of early intolerance and long-term effects of propranolol in dilated cardiomyopathy [J]. J Card Fail,1996,2:273-277.
[20]Di Lenarda A, Demaria R, Gavazzi A, et al. Long-term survival effect of motoprolol in dilated cardiomyopathy.the spic(italian multicentre cardiomyopathy study) group [J]. Heart,1998,79:337-344.
[21]Wiklund I, Waagstein F, Swedberg K, et al. Quality of life on treatment with metoprolol in dilated cardiomyopathy:results from the mdc trial.metoprolol in dilated cardiomyopathy trial [J]. Cardiovasc Dugs Ther,1996,10:361-368.
[22]Podlowski S, Luther HP, Morwinski R, et al. Agonistic anti-betal-adrenergic receptor autoantibodies from cardiomyopathy patients reduce the betal-adrenergic receptor expression in neonatal rat cardiomyocytes [J]. Circulation,1998,98:2470-2476.
[23]Waagstein F. Eficacy of beta blockers in idiopathic dilated cardiomyopathy and ischemic cardiomyopathy [J]. Am J Cardiol,1997,80(9b):45j-49j.
[24]Witte K, Schnecko A, Hauth D, et al. Effects of chronic application of propranolol on betaadrenergic signal transduction in heart ventricles from myopathic bio to2 and control hamsters [J]. Br J Pharmacol,1998,125:1033-1041.
[25]Bristow MT, Abraham WT, Yoshikawa T, et al. Second-and third-generation beta-blocking drugs in chronic heart failure [J]. Cardiovasc Drugs Ther,1997, 11(suppl1):291-296.
[26]Quaife RA, Gilbert EM, Christian PE, et al. Effects of carvedilol on systolic and diastolic left ventricular performance in idiopathic dilated cardiomyopathy or ischemic cardiomyopathy [J]. Am J Cardiol,1996,78:779-784.
[27]Gilbert EM, Abraham WT, Olsen S, et al. Comparative hemodynamic,left ventricular functional,and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart [J]. Circulation,1996,94:2817-2825.
[28]Magnusson Y, Marullo S, Hoyer s, et al. Mapping of a functional epitope on the β1-adrenergic receptor in patients with idiopathic dilated cardiomyopathy [J]. J Clin Invest,1990,86(5):1658-1663.
[29]张麟,胡大一,史旭波,等.心脏β1和M2受体自身抗体和心衰的研究[J].中华内科杂志,2001,40(7)：455-447.
[30]Savino W, Dardenne M. Immune-neuroendocrine interactions. Immune Today, 1995,16(7):318-322.
[31]Jahns R, Boivin V, Hein L, et al.Direct evidence for a β1-adrenergic receptor-directed autommune attack as a cause of idiopathic dilated cardiomyopathy [J]. J Clin Invest, 2004,131(10):1419-1429.
[32]王庸晋,王治平,姜胜,等.卡维地洛对扩张型心肌病心肌β1和M2受体自身抗体的影响.长治医学院学报.2007,
[33]Turhan Kurum, MD, Ersan Tatli, MD, and Mahmut Yuksel, MD. Effects of Carvedilol on Plasma Levels of Pro-Inflammatory Cytokines in Patients with Ischemic and Nonischemic Dilated Cardiomyopathy [J]. Tex Heart Inst J.2007; 34(1): 52-59.
[34]Caforio AL, Bonifacio E, Stewart JT, Neglia D, Parodi O, Bottazzo GF, McKenna WJ. Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy [J]. J Am Coll Cardiol,1990,15:1527-1534.
[35]Fu MLX. Anti-Fu, Anti-M2 muscarinic receptor autoantibodies and idiopathic cardiomyopathy [J]. Int J Cardiol,1996,54(2):127-135.
[36]Liao YH, Functional analysis of autoantibodies against ADP/ATP carrier from dilated cardiomyopathy [J]. Int J Cardiol,1996,54:165-169.
[37]Wallukat G, Reinke P, Dorffel WV, Luther HP, Bestvater K, Felix SB, Baumann G. Removal of autoantibodies in dilated cardiomyopathy by immunoadsorption [J]. Int J Cardiol,1996,54:191-195.
[38]Staudt A, Schaper F, Stangl V, et al. Immunohistological changes in dilated cardiomyopathy induced by immunoadsorption therapy and subsequent immunoglobulin substitution [J]. Circulation,2001,103:2681-2686.
[39]Staudt A, Bohm M, Knebel F, et al. Potential role of autoantibodies belonging to the immunoglobulin G-3 subclass in cardiac dysfunction among patients with dilated cardiomyopathy [J]. Circulation,2002,106:2448-2453.
[40]Staudt A, Staudt Y, Dorr M, et al. Potential role of humoral immunity in cardiac dysfunction of patients suffering from dilated cardiomyopathy. J Am Coll Cardiol 2004,44:829-836.
[41]Konovalov GA, Belenkov IuN, Zvezdkin PV, et al. Apheresis of immunoglobulins-new approach to the treatment of severe dilated cardiomyopathy [J]. Kardiologiia, 2002,42(6):92-6.
[42]Felix SB, Staudt A, Landsberger M, et al. Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption [J]. Am Coll Cardiol,2002,39(4): 646-652.
[43]Larsson Lisa, Mobini Reza, Aukrust Pal, et al. Beneficial effect on cardiac function by intravenous immunoglobulin treatment in patients with dilated cardiomyopathy is not due to neutralization of anti-receptor autoantibody [J]. Autoimmunity, 2004,37,489-493.
[44]Gomberg-Maitland M, Frishman WH.Thyroid hormone and cardiovascular disease [J]. Am heart J,1998,135:187-196.
[45]Klein I, Ojamaa K. Thyroid hormone treatment of congestive heart failure [J]. Am J Cardiol,1998,81:490-491.
[46]Fruhwald FM, Ramschak-Schwarzer S, Pichler B, et al. Subclinical thyroid disorders in patients with dilated cardiomyopathy [J]. Cardiology,1997,88:156-159.
[47]Morkin E, Pennock GD, Raya TE, et al. Development of a thyroid hormone analogie for the treatment of congestive heart failure [J]. Thyroid,1996,6:521-526.
[48]Moruzzi P, Doria E, Agostoni PG, et al. Usefulness of 1-thyroxine ot improve cardiac and exercise performance in idiopathic dilated car-diomyopathy [J]. Am J Cardiol, 1994,73:374-378.
[49]Moruzzi P, Doriz E, Agostoni PG, et al. Medium-term effectiveness of 1-thyroxine treatment in idiopathic dilated cardiomyopathy [J]. Am J Med,1996,101:461-467.
[50]Hamilton MA, Stevenson LW, Fonarow GC, et al. Safety and hemody-namic effects of intravenous triiodothyromine in advanced congestive teart failure [J]. Am J Cardiol, 1998,81:443-447.
[51]Lombardi G, Colao A, Ferone D, et al. Effectof growth hormone on cardiac function [J]. Horm res,1997,48(suppl 4):38-42.
[52]Silverman BL, Friedlander JR. Is growth hormone good for the heart [J]? J pediatr, 1997,131:s70-s74.
[53]Lombardi G, Colao A, Marzullo P, et al. Is growth hormone bad for hour heart? cardiovascular impact of gh deficiency and of acromegaly [J]. J Endocrinol,1997, 155(suppl 1):s33-s37.
[54]Osterziel KJ, Strohm O, Schuler J, et al. Randomised, double-blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy [J]. Lancet,1998,351: 1233-1237.
[55]Fazio S, Sabatini D, Capaldo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomyopathy [J]. N Engl J Med,1996,334:809-814.
[56]Capaldo B, Lembo G, Rendina V, et al. Sympathetic deactivation by growth hormone treatment in patients with dilated cardiomyopathy [J]. Eur Heart J,1998,19:623-627.
[57]Isgaard J, Bergh CH, Caidahl K, et al. A placebo-controlled study of growth hormone in patients with congestive heart failure [J]. Eur Heart J,1998,19:1704-1711.
[58]Kamisago M, Sharma SD, Depalma SR, et al. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy [J]. N Engl J Med,2000,343:1688-1696.
[59]Chang AN, Potter JD. Sarcomeric protein mutations in dilated cardiomyopathy [J]. Heart Fail Rev,2005,10:225-235.
[60]Taylor M, Carniel E, Mestroni L. Cardiomyopathy, familial dilated [J]. Orphanet J Rare Diseases,2006,1:27.
[61]Olson TM, Michels VV, Thibodeau SN, et al.Actin mutations in dilated cardiomyopathy, a heritable form of heart failure [J]. Science,1998,280:750-752.
[62]Kamisago M, Sharma SD, Depalma SR, et al. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy [J]. N Engl J Med,2000,343:1688-1696.
[63]Regitz-Zagrosek V, Daehmlow S, Knueppel T, et al. Novel mutations in theβmyosin heavy chain and myosin binding protein C gene are associated with dilated cardiomyopathy [J]. Circulation,2001,104 Suppl 11:11-572.
[64]Murphy RT, Mogensen J, Shaw A, et al. Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy[J]. Lancet,2004,363:371-372.
[65]Mogensen J, Murphy RT, Shaw A, et al. Cardiac troponin C, and T mutations in 238 patients with idiopathic dilated cardiomyopathy:Prevalence, clinical features and impact on the troponin complex [J]. Circulation,2003,108:IV-50.
[66]Olson TM, Kishimoto NY, Whitby FG, et al. Mutations that alter the surface charge of alpha-tropomyosin are associated with dilated cardiomyopathy [J]. J CmOL Cell Cardiol,2001,33:723-732.
[67]Gerull B, Gramlich M, Athertom J, et al. of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy [J]. Nat Genet,2002,30:201-204.
[68]Li D, Tapscoft T, Gonzalez O, et al. Desmin mutation responsible for idiopathic dilated cardiomyopathy [J]. Circulation,1999,100:461-464.
[69]Tsubata S, Bowles KR, Vatta M, et al. Mutations in the human δ-Sarcoglycan gene in familial and sporadic dilated cardiomyopathy [J]. J Clin Invest,2000,106:655-662.
[70]Olson TM, Illenberger S, Kishimoto NY, et al. Metavinculin mutations alter actin interaction in dilated cardiomyopathy [J]. Circulation,2002,105:431-437.
[71]Towbin JA, Hejtmancik JF, Brink P, et al. X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus [J]. Circulation,1993,87:1854-1865.
[72]D'Adamo P, Fassone L, Gedeon A, et al. The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies [J]. Am J Hum Genet,1997,61:862-867.
[73]Fatkin D, Macrae C, Sasaki T, et al. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction system disease[J]. N Engl J Med,1999,341:1715-1724.
[74]Fatkin D, Graham RM. Molecular mechanisms of inherited cardiomyopathies [J]. Physiol Rev,2002,82:945-980.
[75]Fatkin D, Graham RM. Molecular mechanisms of inherited cardiomyopathies [J]. Physiol Rev,2002,82:945-980.
[76]Aldrin VG, Junor AB, Keita H, et al. Role of troponin T in disease [J]. Molecular and Cellular Biochemistry,2004,263:115-129.
[77]Hinkle A, Goranson A, Butters CA, et al. Roles for the troponin tail domain in thin filament assembly and regulation [J]. J Biol Chem,1999,274:7157-7164.
[78]Villard E, Duboscq-Bido L, Charron P, et al. Mutation screening in dilated cardiomyopathy:prominent role of the beta myosin heavy chain gene [J]. Eur Heart J, 2005,26:794-803.
[79]Li D, Czernuszewicz GZ, Gonzalez O, et al. Novel cardiac troponin T mutation as a cause of familial dilated cardiomyopathy [J]. Circulation,2001,104:2188-2193.
[80]Lu QW, Morimoto S, Harada K, et al. Cardiac troponin T mutation R141W found in dilated cardiomyopathy stabilizes the troponin T-tropomyosin interaction and causes a Ca2+desensitization [J]. J Mol Cell Cardio,2003,35:1421-1427.
[81]Morimoto S, Lu QW, Harada K, et al. Ca2+-desensitizing effect of a deletion mutation Delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy [J]. Proc Natl Acad Sci USA,2002,99:913-918.
[82]冯娟,董伟,全雄志,等.cTnTR141W转基因小鼠扩张型心肌病模型的建立[J].中国比较医学杂志.2007,17：563-567.
[83]蒋青松,黄燮南,周岐新,等.人参皂甙Rbl对PGF2α诱导心肌肥大的作用[J].四
川生理科学杂志,2004,26(4)：181.
[84]Jiang QS, Huang XN, Yang GZ, et al. Inhibitory effect of ginsenoside Rbl on calcineurin signal pathway in cardiomyocyte hypertrophy induced by prostaglandin F2alPha [J]. Acta Pharmacol Sinica,2007,28:1149-1154.
[85]Jiang QS, Huang XN, Dai ZK, et al. Inhibitory effect of ginsenoside Rb1 on cardiac hypertrophy induced by monocrotaline in rat [J]. J Ethnopharmacol,2007,111:567-72.
[86]王薇娜,赵良平,王丽,等.人参皂甙Rbl对大鼠急性心肌梗死后左室重构的影响[J].中国微循环,2006,10(4)：256-258.
[87]王宁元,吕传江,陈学海,等.人参皂甙Rgl诱导骨髓干细胞游走分化促进家兔心肌梗死后心肌血管内皮细胞再生的研究[J].中国中西医结合杂志,2005,25(10)：916-919.
[88]汪朝晖,冼绍祥,杨忠奇,等.人参总皂甙诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].广州中医药大学学报,2006,23(2)：100-103.
[89]刘正湘,刘晓春.人参皂甙Rbl与Re对大鼠缺血再灌注心肌细胞凋亡的影响[J].中国组织化学与细胞化学杂志,2002,11(4)：374-377.
[90]刘艳怪,刘在萍,焦建杰,等.黄芪皂甙Ⅳ对正常和心功能受抑制大鼠左心室心肌力学的影响.中草药,2001,32(4)：332-334.
[91]周吉燕,樊琳,孔建龙,等.黄芪中不同提取成分对在体大鼠心肌缺血-再灌注损伤的心功能影响[J].中国中药杂志,2000,25(5)；300-302.
[92]陈永仲,等.黄芪皂甙甲对小鼠淋巴结内淋巴细胞和巨噬细胞的影响[J].南京医学院学报.1987,7(1)：9.
[93]黄芪皂苷对培养的小鼠腹腔巨噬细胞的激活作用[J].中国病理生理杂志.2008,24(8)：1625-1628.
[94]张召才,杨英珍,李双杰,等.黄芪甲苷对病毒性心肌炎小鼠心肌纤维化的影响.中国新药与临床杂志,2003,22(9)：515-519.
[95]冼绍祥,杨忠奇,汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究.广州中医药大学学报.2007,24(1)：37-40.
[96]柴向枢,王志新,陈平平等.葛根素的抗心律失常作用[J].中国药理学报,1985,6(3)：166.
[97]范礼理,DDO'Keefe, W J Powell,等.葛根素对急性心肌缺血狗区域性心肌血流量与心脏血流动力学的作用[J].药学学报,1984,19(11)：801.
[98]吉宠龙,王天佑.葛根素抑制大鼠背根神经节细胞河豚毒素不敏感钠电流[J],中国药理学报,1996,17(2)：115.
[99]王海燕,彭亚丽.葛根素药理研究进展[J].山东医药工业,2001,20(4)：36-37.
[100]段重高,李宏伟,徐理纳,等.葛根素对金黄地鼠脑微循环的影响[J].中华医学杂志,1991,71(9)：56.
[101]朱庆磊,吕欣然,等.葛根素的药理学和临床应用研究进展[J].中草药,1997,28(11)：693-696.
[102]苏晓灵,王嵘,周白丽,等.葛根素对心肌缺血再灌注损伤保护作用的实验研究[J].临床内科杂志,2004,21(11)：779-781.
[103]刘薇,王亚利,张式暖,等.葛根素对慢性缺氧心肌保护作用的实验研究[J].山东医药,2006,46(5)：15-16.
[104]李法琦,陈运贞.灯盏花素对自发性高血压大鼠心肌细胞凋亡和心室重的影响[J].重庆医科大学学报,2002,27(4)：400.
[105]周浩,陈少贤,王良兴,等.灯盏花素对慢性低氧大鼠PKC的影响[J].中国药理学通报,2002,18(1)：39-42.
[106]任海玲,江时森,谢渡江,等.中药川芎嗪对慢性压力超负荷大鼠心肌纤维化的干预作用[J].中国临床康复,2003,7(12)：1748-1749.
[107]宋德明,苏海,吴美华,等.川芎嗪、丹参对心肌成纤维细胞胶原合成和细胞增殖的影响[J].中国中西医结合杂志,1998,18(7)：423-425.
[108]张冬梅,秦英,杨君,等.川芎嗪对血管紧张素Ⅱ诱导的人al(Ⅰ)胶原基因启动子活性的影响[J].中国中医药信息杂志,2005,12(9)：21-22.
[109]阮长武,张代富,于萍,等.苦参碱对内皮素诱导心肌细胞肥大及肌球蛋白基因表达的影响[J].同济大学学报(医学版),2002,23(4)：271.
[110]王振涛,韩丽华,朱明军,等.川芎嗪注射液促心梗后大鼠缺血心肌血管新生作用及相关生长因子影响的研究[J].辽宁中医杂志,2006,33(7)：888-890.
[111]余乐涵,赵小曼,李华,等.川芎嗪对缺血再灌注后心肌细胞凋亡的影响[J].江西医学院学报,2006,46(3)：27-29.
[112]阮长武,何仲海,金朝俊,等.苦参碱对去甲肾上腺素促心肌细胞肥大及肌球蛋白重链基因表达的影响[J].临床心血管病杂志,2002,18(4)：171-172.
[113]胡迎春,欧阳静萍,李艳琴,等.苦参碱对醛固酮诱导大鼠心肌成纤维细胞细胞周期和增殖细胞核抗原表达的影响[J].武汉大学学报(医学版),2004,25(3)：224.
[114]陆泽安,李庆平,饶曼人,等.粉防已碱对高血压心肌肥厚大鼠心肌胶原含量和肌球蛋白ATP酶活性影响[J].中国药理学与毒理学杂志,2001,15(2)：121-124.
[115]RAO Man-Ren. Effects of tetrandrine on cardiac and vascular remodeling [J]. Acta Pharmacol Sin,2002,23(12):1075-1085.
[116]Rang WQ, Du YH, Hu CP, et al. Protective effects of evodiamine on myocardial ischemia-reperfusion injury in rats[J]. Planta Med,2004,70 (12):1140-1143.
[117]郑敏,吴基良,李立中,等.牛磺酸对肾性高血压大鼠血浆及心肌血管紧张素Ⅱ、醛固酮的影响[J].中国心血管杂志,2003,8(5)：313-315.
[118]黄荣杰,刘唐威,庞玉生.牛磺酸对扩张心肌病大鼠左心室肌转化生长因子p1表达的影响[J].现代诊断与治疗,2004,15(2)：83-85.
[119]阿魏酸钠对心肌细胞缺氧／复氧损伤的保护作用及其机制.药学学报,2004,39(5)：325-327.
[120]李屏,曾秋棠,周彤,等.阿魏酸钠抗心律失常机制的初步探讨.贵州医药,2001,,25(10)：884-886.
[121]Geiger B, Ayalon O. Cadherins [J]. Annu Rev Cell Biol,1992,8:307-332.
[122]Juliano RL, Haskell S. Signal transduction from the extracellular matrix [J]. J Cell Biol,1993,120:577-585.
[123]Perriard JC, Hirschy A, Ehler E. Dilated cardiomyopathy:a disease of the intercalated disc [J]? Trends Cardiovasc Med,2003,13:30-38.
[124]Pellieux C, Foletti A, Peduto G, et al. Dilated cardiomyopathy and impaired cardiac hypertrophic response to angiotensin II in mice lacking FGF-2 [J]. J Clin Invest,2001,108:1843-1851.
[125]Zhang H, Sunnarborg SW, Faber JE. Heparin-Binding EGF-Like Growth Factor (HB-EGF) mediates low flow-induced negative hypertrophic remodeling (FINR) but not high flow-induced positive eutrophic remodeling (FIPR) of carotid artery [J]. Circulation,2006,114:217-223.
[126]Erin E, Tansey BS, Kevin F, et al. Reduction and redistribution of gap and adherens junction proteins after ischemia and reperfusion [J]. Ann Thorac Surg,2006, 82(4):1472-1479.
[127]Hagendorff A, Schumacher B, Kirchhoff S, et al. Conduction disturbances and increased atrial vulnerability in connexin 40 deficent mice analyzed by transesophyageal stimulation [J]. Circulation,1999,99:1508-1515.
[128]Ferreira-Cornwell MC, Luo Y, Narula N, et al. Remodeling the intercalated disc leads to cardiomyopathy in mice misexpressing cadherins in the heart [J]. J Cell Sci, 2002,115:1623-1634.
[129]Brancaccio M, Hirsch E, Notte A, et al. Integrin signalling:the tug-of-war in heart hypertrophy [J]. Cardiovasc Res,2006,70:422-433.
[130]Srivastava D, Yu S. Stretching to meet needs:integrin-linked kinase and the cardiac pump [J]. Genes Dev,2006,20:2361-72.
[131]Bouzeghrane F, Mercure C, Reudelhuber TL, et al. Alpha8betal integrin is upregulated in myofibroblasts of fibrotic and scarring myocardium [J]. J Mol Cell Cardiol,2004,36:343-353.
[132]Li J, Mayne R, Wu C. A novel muscle-specific β1 integrin binding protein (MIBP) that modulates myogenic differentiation [J]. J Cell Biol,1999,147:1391-1398.
[133]Nojiri H, Shimizu T, Funakoshi M, et al. Oxidative stress causes heart failure with impaired mitochondrial respiration [J]. J Biol Chem,2006,281:33789-33801.
[134]Lu QW, Morimoto S, Harada K, et al. Cardiac troponin T mutation R141W found in dilated cardiomyopathy stabilizes the troponin T-tropomyosin interaction and causes a Ca2+ desensitization [J]. J Mol Cell Cardiol,2003,35:1421-1427.
[135]Valencik ML, Zhang DF, Punske B, et al. Integrin activation in the heart:a link between electrical and contractile dysfunction [J]? Circ Res,2006,99:1403-1410.
[136]付金容,唐其柱,沈涤非,等.整合素β1在自身免疫性心肌炎小鼠心肌的表达[J].心脏杂志,2005,17(1)：25-28.
[137]Fujino T, Hasebe N, Fujita M, et al. Enhanced expression of heparin-binding EGF-like growth factor and its receptor in hypertrophied left ventricle of spontaneously hypertensive rats [J]. Cardiovasc Res,1998,38:365-374.
[138]Iwabu A, Murakami T, Kusachi S, et al. Concomitant expression of heparin-binding epidermal growth factor-like growth factor mRNA and basic fibroblast growth factor mRNA in myocardial infarction in rats [J]. Basic Res Cardiol, 2002,97:214-222.
[139]Ushikoshi H, Takahashi T, Chen XH, et al. Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes [J]. Lab Invest,2005,85:862-873.
[140]Yoshioka J, Prince RN, Huang H, et al. Cardiomyocyte hypertrophy and degradation of connexin43 through spatially restricted autocrine/paracrine heparin-binding EGF [J]. PNAS,2005,102:10622-10627.
[141]Asakura M, Kitakaze M, Takashima S, et al. Cardiac hypertrophy is inhibited by antagonism of ADAM 12 processing of HB-EGF:metalloproteinase inhibitors as a new therapy [J]. Nature Med,2002,8:35-40.
[142]Lee KS, Park JH, Lee S, et al. HB-EGF induces delayed STAT3 activation via NF-kappaB mediated IL-6 secretion in vascular smooth muscle cell [J]. Biochim Biophys Acta,2007,1773:1637-44.
[143]Ng DC, Court NW, dos Remedios CG, et al. Activation of signal transducer and activator of transcription (STAT) pathways in failing human hearts [J]. Cardiovasc Res,2003,57:333-346.
[144]Sun LG, Ma KW, Wang HX, et al. JAK1-STAT1-STAT3, a key pathway promoting proliferation and preventing premature differentiation of myoblasts [J]. J Cell Biol,2007,179:129-138.
[145]Yamauchi-Takihara K, Kishimoto T. A novel role for STAT3 in cardiac remodeling [J]. Trends Cardiovasc Med,2000,10:298-303.
[146]Yamauchi-Takihara K, Kishimoto T. Cytokines and their receptors in cardiovascular diseases-role of gp130 signaling pathway in cardiac myocyte growth and maintenance [J]. Int J Exp Pathol,2000,81:1-16.
[147]Kunisada K, Negoro S, Tone E, et al. Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin-induced cardiomyopathy [J]. PNAS,2000,97:315-319.
[148]Negoro S, Kunisada K, Fujio Y, et al. Activation of signal transducer and activator of transcription 3 protects cardiomyocytes from hypoxia/ reoxygenation-induced oxidative stress through the upregulation of manganese superoxide dismutase [J]. Circulation,2001,104:979-981.
[149]Ku L, Feiger L, Taylor M, et al. Familial dilated cardiomyopathy [J]. Circulation, 2003,108:e118-e121.
[150]O'Connell JB, Moore CK, Waterer HC. Treatment of end stage dilated cardiomyopathy [J]. Br Heart J,1994,72 (Supplement):S 52-S 56.Massin EK. Current treatment of dilated cardiomyopathy [J]. Texas Heart Institute Journal,1991, 18:41-49.
[151]Attele AS, Wu JA, Yuan CS, et al. Ginseng pharmacology:multiple constituents and multiple actions [J]. Biochem Pharmacol,1999,58:1685-1693.
1.邓江,吴芹,黄燮南.川芎嗪对大鼠压力超负荷心肌细胞外信号调节激酶1mRNA表达的抑制作用.中国药理学与毒理学杂志,2008,22：336-340.
2.蒋青松，黄燮南,戴支凯,等.川芎嗪对PGF2α诱导心肌肥大的抑制作用.中药药理与临床,2005,21：9-11.
3.任海玲,江时森,谢渡江,等.中药川芎嗪对慢性压力超负荷大鼠心肌纤维化的干预作用[J].中国临床康复,2003,7(12)：1748-1749.
4.宋德明,苏海,吴美华,等.川芎嗪、丹参对心肌成纤维细胞胶原合成和细胞增殖的影响[J].中国中西医结合杂志,1998,18(7)：423-425.
5.郭自强,牛福玲.川芎嗪对血管紧张素Ⅱ致心肌肥大的影响[J].北京中医药大学学报,2001,24(3)：32-34.
6.张冬梅,秦英,杨君,等.川芎嗪对血管紧张素Ⅱ诱导的人al(Ⅰ)胶原基因启动子活性的影响[J].中国中医药信息杂志,2005,12(9)：21-22.
7. 王振涛,韩丽华,朱明军,等.川芎嗪注射液促心梗后大鼠缺血心肌血管新生作用及相关生长因子影响的研究[J].辽宁中医杂志,2006,33(7)：888-890.
8.余乐涵,赵小曼,李华,等。川芎嗪对缺血再灌注后心肌细胞凋亡的影响[J].江西医学院学报,2006,46(3)：27-29.
9. Hintz KK, Ren J (2003). Tetramethylpyrazine elicits disparate responses in cardiac contraction and intracellular Ca(2+) transients in isolated adult rat ventricular myocytes. Vascular Pharmacology 40:213-217.
10. Sheu JR, Kan YC, Hung WC, Lin CH, Yen MH (2000). The antiplatelet activity of tetramethylpyrazine is mediated through activation of NO synthase. Life Sci 67: 937-947.
11. Lin CI, Wu SL, Tao PL, Chen HM, Wei J (1993). The role of cyclic AMP and phosphodiesterase activity in the mechanism of action of tetramethylpyrazine on human and dog cardiac and dog coronary arterial tissues. J Pharm Pharmacol 45: 963-966.
12. Shih YH, Wu SL, Chiou WF, Ku HH, Ko TL, Fu YS (2002). Protective effects of tetramethylpyrazine on kainate-induced excitotoxicity in hippocampal culture. Neuroreport 13:515-519.
13. Zhang Z, Wei T, Hou J, Li G, Yu S, Xin W (2003). Tetramethylpyrazine scavenges superoxide anion and decreases nitric oxide production in human polymorphonuclear leukocytes. Life Sci 72:2465-2472.
14. Sutter MC, Wang YX. (1993). Recent cardiovascular drugs from Chinese medicinal plants. Cardiovasc Res 27:1891-1901.
15. Zhang ZH, Yu SZ, Wang ZT, Zhao BL, Hou JW, Yang FJ, et al. (1994). Scavenging effects of tetramethylpyrazine on active oxygen free radicals. Acta Pharmacol Sin 5: 229-231.
16.赵玉清,笔雪艳.磷酸川芎嗪注射液药理毒理研究综述.时珍国医国药.2007,7.
17. Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure[J]. Eur Heart J,2001,22,1527-1560.
18.黄斌.扩张性心肌病患者血浆BNP水平与左心功能关系的研究.临床医学工程,2008,5：9.
19. Rupp H, Jacob R. Myocardial transitions between fast-and slow-type muscle as monitored by the population of myosin isoenzymes [A]. In:Rupp H, ed. Regulation of heart function [M]. New York:Thieme Inc.,1986:271-291.
20. Salmikangas P, van der Ven PF, Lalowski M, Taivainen A, Zhao F, Suila H, et al. (2003). Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly. Hum Mol Genet 12: 189-203.
21. Zeller R, Ivandic BT, Ehlermann P, Mucke O, Zugck C, Remppis A, et al. (2006). Large-scale mutation screening in patients with dilated or hypertrophic cardiomyopathy:a pilot study using DGGE. J Mol Med 84:682-691.
22. Hauser MA, Horrigan SK, Salmikangas P, Torian UM, Viles KD, Dancel R, et al. (2000). Myotilin is mutated in limb girdle muscular dystrophy 1A. Hum Mol Genet 9: 2141-2147.
23. Hauser MA, Conde CB, Kowaljow V, Zeppa G, Taratuto AL, Torian UM, et al. (2002). Myotilin mutation found in second pedigree with LGMD1A. Am J Hum Genet,71,1428-1482.
24. Garvey SM, Liu Y, Miller SE, Hauser MA (2008). Myotilin overexpression enhances myopathology in the LGMD1A mouse model. Muscle Nerve 37:663-7.
25. Moza M, Mologni L, Trokovic R, Faulkner G, Partanen J, Carpen O (2007). Targeted Deletion of the Muscular Dystrophy Gene myotilin Does Not Perturb Muscle Structure or Function in Mice. Mol Cell Biol.27:244-252.
26. Flavigny J, Richard P, Isnard R, Carrier L, Charron P, Bonne G et al., (1998). Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy. J Mol Med 76:208-214.
27. Margossian SS, White HD, Caulfield JB, Norton P, Taylor S, Slayter HS (1992). Light chain 2 profile and activity of human ventricular myosin during dilated cardiomyopathy. Identification of a causal agent for impaired myocardial function. Circulation 85:1720-1733.
28. Corbett JM, Why HJ, Wheeler CH, Richardson PJ, Archard LC, Yacoub MH et al. (1998). Cardiac protein abnormalities in dilated cardiomyopathy detected by two-dimensional polyacrylamide gel electrophoresis. Electrophoresis 19:2031-2042.
29. Chen J, Kubalak SW, Minamisawa S, Price RL, Becker KD, Hickey R et al. (1998). Selective requirement of myosin light chain 2v in embryonic heart function. J Biol Chem 273:1252-1256.
30. Morano I. Tuning the human heart molecular motors by myosin light chains. J Mol Med 1999,77:544-555.
31. Davis JS, Hassanzadeh S, Winitsky S, Lin H, Satorius C, Vemuri R, et al. The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation. Cell,2001,107:631641.
32. Morano I. Effects of different expression and posttranslational modifications of myosin light chains on contractility of skinned human cardiac fibers. Basic Res Cardiol,1992,87:129-141.
33. Sanbe A, Fewell JG, Gulick J, Osinska H, Lorenz J, Hall DG, et al. Abnormal Cardiac Structure and Function in Mice Expressing Nonphosphorylatable Cardiac Regulatory Myosin Light Chain 2. J Biol Chem,1999,274:21085-21094.
34. Zhang T and Brown JH. Role of Ca2+/calmodulin-dependent protein kinase Ⅱ in cardiac hypertrophy and heart failure, Cardiovasc Res,2004,63:476-486.
35. Zhang R, Khoo MS, Wu Y, Yang Y, Grueter CE, Ni G et al. Calmodulin kinase Ⅱ inhibition protects against structural heart disease, Nat Med,2005,11:409-417.
[1]Koseki T, Inohara N, Chen S, et al. ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases [J].Proc Natl Acad Sci USA,1998,95(9):5156-5160.
[2]Geertman R, McMahon A, Sabban EL. Cloning and characterization of cDNAs for novel proteins with glutamic acidproline dipeptide tandem repeats[J]. Biochim Biophys Acta,1996,1306:147-152.
[3]Abmayr S, Crawford RW, Chamberlain JS. Characterization of ARC, apoptosis repressor interacting with CARD, in normal and dystrophin—deficient skeletal muscle[J]. Hum Mol Genet,2004,13:213—221.
[4]Donath S, Li PF, Willenbockel C, et al. Apoptosis repressor with caspase recruitment domain is required for cardioprotection in response to biomechanical and ischemic stress[J]. Circulation,2006,113:1203-1212.
[5]Gustafsson AB, Sayen MR, Williams SD, et al. TAT protein transduction into isolated perfused hearts, TAT-apoptosis repressor with caspase recruitment domain is cardioprotective[J]. Circulation,2002,106:735-739.
[6]Yaniv G, Shilkrut M, Larisch S, et al. Hydrogen peroxide predisposes neonatal rat ventricular myocytes to Fas-mediated apoptosis[J]. Biochem Biophys Res Commun, 2005,336(3):740-746.
[7]Ekhterae D, Lin Z, Lundberg MS, et al. ARC inhibits cytochrome c release from mitochondria and protects against hypoxia-induced apoptosis in heart-derived H9c2 cells[J]. Circ Res,1999,85(12):e70-77.
[8]Neuss M, Monticone R, Lundberg MS, et al. The apoptotic regulatory protein ARC (apoptosis repressor with caspase recruitment domain) prevents oxidant stress-mediated cell death by preserving mitochondrial function[J]. J Biol Chem,2001, 276 (36):33915-33922.
[9]Nam Y J, Mani K, Ashton AW, et al. Inhibition of both the extrinsic and intrinsic death pathways through nonhomotypic death-fold interactions [J]. Mol Cell,2004, 15(6):901-912.
[10]李玉珍.心脏特异性高度表达的抗凋亡蛋白—ARC[J].生物化学与生物物理进展.2006,33(9)：816-819.
[11]Gustafsson AB, Tsai JG, Logue SE, et al. Apoptosis repressor with caspase recruitment domain protects against cell death by interfering with Bax activation[J]. J Biol Chem,2004,279(20):21233-21238.
[12]Jo DG, Jun JI, Chang JW, et al. Calcium binding of ARC mediates regulation of caspase 8 and cell death[J]. Mol Cell Biology,2004,24 (22):9763-9769.
[13]Ekhterae D, Platoshyn O, Zhang S, et al. Apoptosis repressor with caspase domain inhibits cardiomyocyte apoptosis by reducing K+currents[J]. Am J Physiol Cell Physiol,2003,284:1405-1410.
[2]Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies [J]. Circulation,2006,113:1807-1816.
[3]Ho KK, Anderson KM, Kannel WB, et al. Survival after the onset of congestive heart failure in Framingham heart study subjects [J]. Circulation,1993,88:107-115.
[4]Takahashi M, Takeda S, Kurokawa S, et al. Cyclic GMP production by ANP, BNP, and NO during worsening and improvement of chronic heart failure [J]. Jpn Heart, 2003,44(5):713-24.
[5]Vogt AM, Kubler W. Heart failure:is there an energy deficit contributing to contractile dysfunction [J]. Basic Res Cardiol,1998,93(1):1-10.
[6]Beckemeier ME, Bora PS. Fatty acid ethyl esters:potentially toxic products of myocardial ethanol metabolism [J]. Mol Cell Cardiol,1998,30(11):2487-94.
[7]Ikeda Y, Yamada M, Matsuzaki M,et al. Multicenter clinical trial of angiotensin receptor blocker in patients with chronic heart failure:review of recent clinical trial [J]. Nippon Rinsho,2002,60(10):2028-33.
[8]Umemoto S, Kawahara S, Hashimoto R, et al.Angiotensin receptor blockers in chronic heart failure [J]. Nippon Rinsho,2003,61(9):1683-9.
[9]白洁,张国辉.醛固酮受体拮抗剂在扩张型心肌病中的应用.心血管病学进展,2006,27(6)：
[10]Bevilacqua M, Salio M, Cardano P, et al. Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure:the Valsartan Heart Failure Trial (Val-HeFT) [J]. Circulation,2002,106(19):2454-8.
[11]Klein L, O'Connor CM, Gattis WA, et al. Pharmacologic therapy for patients with chronic heart failure and reduced systolic function:review of trials and practical considerations [J]. Am J Cardiol,2003,91(9A):18F-40F.
[12]Elkayam U. Calcium channel blockers in heart failure [J]. Cardiology,1998,89(suppl 1):38-46.
[13]Figulla HR. Gietzen F, Zeymer U, et al. Diltiazem improves cardiac func-tion and exercise capacity in patients with idiopathic dilated cardiomyopa-thy.results of the diltiazem in dilated cardiomyopathy trial [J]. Circulation,1996,94:346-352.
[14]Packer M, O'connor CM, Ghali JK, et al. Effect of amoldipine on morgidity and mortality in severe chronic heart failure.prospective randomized amlodipine survival evaluation study group [J]. N Engl J Med,1996,335:1107-1114.
[15]Zhang X, Hintze TH. Amlodipine releases nitric oxide from canine coronary microvessels:an unexpected mechanism of action of a calcium channel-blocking agent [J]. Circulation,1998,97:576-580.
[16]Mohler ER, Sorensen LC, Fhali JK, et al. Role of cytokines in the mechanism of acton of amlodipine:the praise heart failure trial [J]. J Am Coll Cardiol,1997,30: 34-41.
[17]Constant J. A review of why and how we may use β-blockers in congestive heart failure [J]. Chest,1998,113:800-808.
[18]Waagstein F, Bristow MR, Swedberg K, et al. Beneficial effect of metoprolol in idiopathic dilated cardiomypathy [J]. Lancet,1993,342:1441-1446.
[19]Talwar KK, Bhrargava B, Upasani PT, et al. Hemodynamic predictors of early intolerance and long-term effects of propranolol in dilated cardiomyopathy [J]. J Card Fail,1996,2:273-277.
[20]Di Lenarda A, Demaria R, Gavazzi A, et al. Long-term survival effect of motoprolol in dilated cardiomyopathy.the spic(italian multicentre cardiomyopathy study) group [J]. Heart,1998,79:337-344.
[21]Wiklund I, Waagstein F, Swedberg K, et al. Quality of life on treatment with metoprolol in dilated cardiomyopathy:results from the mdc trial.metoprolol in dilated cardiomyopathy trial [J]. Cardiovasc Dugs Ther,1996,10:361-368.
[22]Podlowski S, Luther HP, Morwinski R, et al. Agonistic anti-betal-adrenergic receptor autoantibodies from cardiomyopathy patients reduce the betal-adrenergic receptor expression in neonatal rat cardiomyocytes [J]. Circulation,1998,98:2470-2476.
[23]Waagstein F. Eficacy of beta blockers in idiopathic dilated cardiomyopathy and ischemic cardiomyopathy [J]. Am J Cardiol,1997,80(9b):45j-49j.
[24]Witte K, Schnecko A, Hauth D, et al. Effects of chronic application of propranolol on betaadrenergic signal transduction in heart ventricles from myopathic bio to2 and control hamsters [J]. Br J Pharmacol,1998,125:1033-1041.
[25]Bristow MT, Abraham WT, Yoshikawa T, et al. Second-and third-generation beta-blocking drugs in chronic heart failure [J]. Cardiovasc Drugs Ther,1997, 11(suppl1):291-296.
[26]Quaife RA, Gilbert EM, Christian PE, et al. Effects of carvedilol on systolic and diastolic left ventricular performance in idiopathic dilated cardiomyopathy or ischemic cardiomyopathy [J]. Am J Cardiol,1996,78:779-784.
[27]Gilbert EM, Abraham WT, Olsen S, et al. Comparative hemodynamic,left ventricular functional,and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart [J]. Circulation,1996,94:2817-2825.
[28]Magnusson Y, Marullo S, Hoyer s, et al. Mapping of a functional epitope on the β1-adrenergic receptor in patients with idiopathic dilated cardiomyopathy [J]. J Clin Invest,1990,86(5):1658-1663.
[29]张麟,胡大一,史旭波,等.心脏β1和M2受体自身抗体和心衰的研究[J].中华内科杂志,2001,40(7)：455-447.
[30]Savino W, Dardenne M. Immune-neuroendocrine interactions. Immune Today, 1995,16(7):318-322.
[31]Jahns R, Boivin V, Hein L, et al.Direct evidence for a β1-adrenergic receptor-directed autommune attack as a cause of idiopathic dilated cardiomyopathy [J]. J Clin Invest, 2004,131(10):1419-1429.
[32]王庸晋,王治平,姜胜,等.卡维地洛对扩张型心肌病心肌β1和M2受体自身抗体的影响.长治医学院学报.2007,
[33]Turhan Kurum, MD, Ersan Tatli, MD, and Mahmut Yuksel, MD. Effects of Carvedilol on Plasma Levels of Pro-Inflammatory Cytokines in Patients with Ischemic and Nonischemic Dilated Cardiomyopathy [J]. Tex Heart Inst J.2007; 34(1): 52-59.
[34]Caforio AL, Bonifacio E, Stewart JT, Neglia D, Parodi O, Bottazzo GF, McKenna WJ. Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy [J]. J Am Coll Cardiol,1990,15:1527-1534.
[35]Fu MLX. Anti-Fu, Anti-M2 muscarinic receptor autoantibodies and idiopathic cardiomyopathy [J]. Int J Cardiol,1996,54(2):127-135.
[36]Liao YH, Functional analysis of autoantibodies against ADP/ATP carrier from dilated cardiomyopathy [J]. Int J Cardiol,1996,54:165-169.
[37]Wallukat G, Reinke P, Dorffel WV, Luther HP, Bestvater K, Felix SB, Baumann G. Removal of autoantibodies in dilated cardiomyopathy by immunoadsorption [J]. Int J Cardiol,1996,54:191-195.
[38]Staudt A, Schaper F, Stangl V, et al. Immunohistological changes in dilated cardiomyopathy induced by immunoadsorption therapy and subsequent immunoglobulin substitution [J]. Circulation,2001,103:2681-2686.
[39]Staudt A, Bohm M, Knebel F, et al. Potential role of autoantibodies belonging to the immunoglobulin G-3 subclass in cardiac dysfunction among patients with dilated cardiomyopathy [J]. Circulation,2002,106:2448-2453.
[40]Staudt A, Staudt Y, Dorr M, et al. Potential role of humoral immunity in cardiac dysfunction of patients suffering from dilated cardiomyopathy. J Am Coll Cardiol 2004,44:829-836.
[41]Konovalov GA, Belenkov IuN, Zvezdkin PV, et al. Apheresis of immunoglobulins-new approach to the treatment of severe dilated cardiomyopathy [J]. Kardiologiia, 2002,42(6):92-6.
[42]Felix SB, Staudt A, Landsberger M, et al. Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption [J]. Am Coll Cardiol,2002,39(4): 646-652.
[43]Larsson Lisa, Mobini Reza, Aukrust Pal, et al. Beneficial effect on cardiac function by intravenous immunoglobulin treatment in patients with dilated cardiomyopathy is not due to neutralization of anti-receptor autoantibody [J]. Autoimmunity, 2004,37,489-493.
[44]Gomberg-Maitland M, Frishman WH.Thyroid hormone and cardiovascular disease [J]. Am heart J,1998,135:187-196.
[45]Klein I, Ojamaa K. Thyroid hormone treatment of congestive heart failure [J]. Am J Cardiol,1998,81:490-491.
[46]Fruhwald FM, Ramschak-Schwarzer S, Pichler B, et al. Subclinical thyroid disorders in patients with dilated cardiomyopathy [J]. Cardiology,1997,88:156-159.
[47]Morkin E, Pennock GD, Raya TE, et al. Development of a thyroid hormone analogie for the treatment of congestive heart failure [J]. Thyroid,1996,6:521-526.
[48]Moruzzi P, Doria E, Agostoni PG, et al. Usefulness of 1-thyroxine ot improve cardiac and exercise performance in idiopathic dilated car-diomyopathy [J]. Am J Cardiol, 1994,73:374-378.
[49]Moruzzi P, Doriz E, Agostoni PG, et al. Medium-term effectiveness of 1-thyroxine treatment in idiopathic dilated cardiomyopathy [J]. Am J Med,1996,101:461-467.
[50]Hamilton MA, Stevenson LW, Fonarow GC, et al. Safety and hemody-namic effects of intravenous triiodothyromine in advanced congestive teart failure [J]. Am J Cardiol, 1998,81:443-447.
[51]Lombardi G, Colao A, Ferone D, et al. Effectof growth hormone on cardiac function [J]. Horm res,1997,48(suppl 4):38-42.
[52]Silverman BL, Friedlander JR. Is growth hormone good for the heart [J]? J pediatr, 1997,131:s70-s74.
[53]Lombardi G, Colao A, Marzullo P, et al. Is growth hormone bad for hour heart? cardiovascular impact of gh deficiency and of acromegaly [J]. J Endocrinol,1997, 155(suppl 1):s33-s37.
[54]Osterziel KJ, Strohm O, Schuler J, et al. Randomised, double-blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy [J]. Lancet,1998,351: 1233-1237.
[55]Fazio S, Sabatini D, Capaldo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomyopathy [J]. N Engl J Med,1996,334:809-814.
[56]Capaldo B, Lembo G, Rendina V, et al. Sympathetic deactivation by growth hormone treatment in patients with dilated cardiomyopathy [J]. Eur Heart J,1998,19:623-627.
[57]Isgaard J, Bergh CH, Caidahl K, et al. A placebo-controlled study of growth hormone in patients with congestive heart failure [J]. Eur Heart J,1998,19:1704-1711.
[58]Kamisago M, Sharma SD, Depalma SR, et al. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy [J]. N Engl J Med,2000,343:1688-1696.
[59]Chang AN, Potter JD. Sarcomeric protein mutations in dilated cardiomyopathy [J]. Heart Fail Rev,2005,10:225-235.
[60]Taylor M, Carniel E, Mestroni L. Cardiomyopathy, familial dilated [J]. Orphanet J Rare Diseases,2006,1:27.
[61]Olson TM, Michels VV, Thibodeau SN, et al.Actin mutations in dilated cardiomyopathy, a heritable form of heart failure [J]. Science,1998,280:750-752.
[62]Kamisago M, Sharma SD, Depalma SR, et al. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy [J]. N Engl J Med,2000,343:1688-1696.
[63]Regitz-Zagrosek V, Daehmlow S, Knueppel T, et al. Novel mutations in theβmyosin heavy chain and myosin binding protein C gene are associated with dilated cardiomyopathy [J]. Circulation,2001,104 Suppl 11:11-572.
[64]Murphy RT, Mogensen J, Shaw A, et al. Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy[J]. Lancet,2004,363:371-372.
[65]Mogensen J, Murphy RT, Shaw A, et al. Cardiac troponin C, and T mutations in 238 patients with idiopathic dilated cardiomyopathy:Prevalence, clinical features and impact on the troponin complex [J]. Circulation,2003,108:IV-50.
[66]Olson TM, Kishimoto NY, Whitby FG, et al. Mutations that alter the surface charge of alpha-tropomyosin are associated with dilated cardiomyopathy [J]. J CmOL Cell Cardiol,2001,33:723-732.
[67]Gerull B, Gramlich M, Athertom J, et al. of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy [J]. Nat Genet,2002,30:201-204.
[68]Li D, Tapscoft T, Gonzalez O, et al. Desmin mutation responsible for idiopathic dilated cardiomyopathy [J]. Circulation,1999,100:461-464.
[69]Tsubata S, Bowles KR, Vatta M, et al. Mutations in the human δ-Sarcoglycan gene in familial and sporadic dilated cardiomyopathy [J]. J Clin Invest,2000,106:655-662.
[70]Olson TM, Illenberger S, Kishimoto NY, et al. Metavinculin mutations alter actin interaction in dilated cardiomyopathy [J]. Circulation,2002,105:431-437.
[71]Towbin JA, Hejtmancik JF, Brink P, et al. X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus [J]. Circulation,1993,87:1854-1865.
[72]D'Adamo P, Fassone L, Gedeon A, et al. The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies [J]. Am J Hum Genet,1997,61:862-867.
[73]Fatkin D, Macrae C, Sasaki T, et al. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction system disease[J]. N Engl J Med,1999,341:1715-1724.
[74]Fatkin D, Graham RM. Molecular mechanisms of inherited cardiomyopathies [J]. Physiol Rev,2002,82:945-980.
[75]Fatkin D, Graham RM. Molecular mechanisms of inherited cardiomyopathies [J]. Physiol Rev,2002,82:945-980.
[76]Aldrin VG, Junor AB, Keita H, et al. Role of troponin T in disease [J]. Molecular and Cellular Biochemistry,2004,263:115-129.
[77]Hinkle A, Goranson A, Butters CA, et al. Roles for the troponin tail domain in thin filament assembly and regulation [J]. J Biol Chem,1999,274:7157-7164.
[78]Villard E, Duboscq-Bido L, Charron P, et al. Mutation screening in dilated cardiomyopathy:prominent role of the beta myosin heavy chain gene [J]. Eur Heart J, 2005,26:794-803.
[79]Li D, Czernuszewicz GZ, Gonzalez O, et al. Novel cardiac troponin T mutation as a cause of familial dilated cardiomyopathy [J]. Circulation,2001,104:2188-2193.
[80]Lu QW, Morimoto S, Harada K, et al. Cardiac troponin T mutation R141W found in dilated cardiomyopathy stabilizes the troponin T-tropomyosin interaction and causes a Ca2+desensitization [J]. J Mol Cell Cardio,2003,35:1421-1427.
[81]Morimoto S, Lu QW, Harada K, et al. Ca2+-desensitizing effect of a deletion mutation Delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy [J]. Proc Natl Acad Sci USA,2002,99:913-918.
[82]冯娟,董伟,全雄志,等.cTnTR141W转基因小鼠扩张型心肌病模型的建立[J].中国比较医学杂志.2007,17：563-567.
[83]蒋青松,黄燮南,周岐新,等.人参皂甙Rbl对PGF2α诱导心肌肥大的作用[J].四
川生理科学杂志,2004,26(4)：181.
[84]Jiang QS, Huang XN, Yang GZ, et al. Inhibitory effect of ginsenoside Rbl on calcineurin signal pathway in cardiomyocyte hypertrophy induced by prostaglandin F2alPha [J]. Acta Pharmacol Sinica,2007,28:1149-1154.
[85]Jiang QS, Huang XN, Dai ZK, et al. Inhibitory effect of ginsenoside Rb1 on cardiac hypertrophy induced by monocrotaline in rat [J]. J Ethnopharmacol,2007,111:567-72.
[86]王薇娜,赵良平,王丽,等.人参皂甙Rbl对大鼠急性心肌梗死后左室重构的影响[J].中国微循环,2006,10(4)：256-258.
[87]王宁元,吕传江,陈学海,等.人参皂甙Rgl诱导骨髓干细胞游走分化促进家兔心肌梗死后心肌血管内皮细胞再生的研究[J].中国中西医结合杂志,2005,25(10)：916-919.
[88]汪朝晖,冼绍祥,杨忠奇,等.人参总皂甙诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].广州中医药大学学报,2006,23(2)：100-103.
[89]刘正湘,刘晓春.人参皂甙Rbl与Re对大鼠缺血再灌注心肌细胞凋亡的影响[J].中国组织化学与细胞化学杂志,2002,11(4)：374-377.
[90]刘艳怪,刘在萍,焦建杰,等.黄芪皂甙Ⅳ对正常和心功能受抑制大鼠左心室心肌力学的影响.中草药,2001,32(4)：332-334.
[91]周吉燕,樊琳,孔建龙,等.黄芪中不同提取成分对在体大鼠心肌缺血-再灌注损伤的心功能影响[J].中国中药杂志,2000,25(5)；300-302.
[92]陈永仲,等.黄芪皂甙甲对小鼠淋巴结内淋巴细胞和巨噬细胞的影响[J].南京医学院学报.1987,7(1)：9.
[93]黄芪皂苷对培养的小鼠腹腔巨噬细胞的激活作用[J].中国病理生理杂志.2008,24(8)：1625-1628.
[94]张召才,杨英珍,李双杰,等.黄芪甲苷对病毒性心肌炎小鼠心肌纤维化的影响.中国新药与临床杂志,2003,22(9)：515-519.
[95]冼绍祥,杨忠奇,汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究.广州中医药大学学报.2007,24(1)：37-40.
[96]柴向枢,王志新,陈平平等.葛根素的抗心律失常作用[J].中国药理学报,1985,6(3)：166.
[97]范礼理,DDO'Keefe, W J Powell,等.葛根素对急性心肌缺血狗区域性心肌血流量与心脏血流动力学的作用[J].药学学报,1984,19(11)：801.
[98]吉宠龙,王天佑.葛根素抑制大鼠背根神经节细胞河豚毒素不敏感钠电流[J],中国药理学报,1996,17(2)：115.
[99]王海燕,彭亚丽.葛根素药理研究进展[J].山东医药工业,2001,20(4)：36-37.
[100]段重高,李宏伟,徐理纳,等.葛根素对金黄地鼠脑微循环的影响[J].中华医学杂志,1991,71(9)：56.
[101]朱庆磊,吕欣然,等.葛根素的药理学和临床应用研究进展[J].中草药,1997,28(11)：693-696.
[102]苏晓灵,王嵘,周白丽,等.葛根素对心肌缺血再灌注损伤保护作用的实验研究[J].临床内科杂志,2004,21(11)：779-781.
[103]刘薇,王亚利,张式暖,等.葛根素对慢性缺氧心肌保护作用的实验研究[J].山东医药,2006,46(5)：15-16.
[104]李法琦,陈运贞.灯盏花素对自发性高血压大鼠心肌细胞凋亡和心室重的影响[J].重庆医科大学学报,2002,27(4)：400.
[105]周浩,陈少贤,王良兴,等.灯盏花素对慢性低氧大鼠PKC的影响[J].中国药理学通报,2002,18(1)：39-42.
[106]任海玲,江时森,谢渡江,等.中药川芎嗪对慢性压力超负荷大鼠心肌纤维化的干预作用[J].中国临床康复,2003,7(12)：1748-1749.
[107]宋德明,苏海,吴美华,等.川芎嗪、丹参对心肌成纤维细胞胶原合成和细胞增殖的影响[J].中国中西医结合杂志,1998,18(7)：423-425.
[108]张冬梅,秦英,杨君,等.川芎嗪对血管紧张素Ⅱ诱导的人al(Ⅰ)胶原基因启动子活性的影响[J].中国中医药信息杂志,2005,12(9)：21-22.
[109]阮长武,张代富,于萍,等.苦参碱对内皮素诱导心肌细胞肥大及肌球蛋白基因表达的影响[J].同济大学学报(医学版),2002,23(4)：271.
[110]王振涛,韩丽华,朱明军,等.川芎嗪注射液促心梗后大鼠缺血心肌血管新生作用及相关生长因子影响的研究[J].辽宁中医杂志,2006,33(7)：888-890.
[111]余乐涵,赵小曼,李华,等.川芎嗪对缺血再灌注后心肌细胞凋亡的影响[J].江西医学院学报,2006,46(3)：27-29.
[112]阮长武,何仲海,金朝俊,等.苦参碱对去甲肾上腺素促心肌细胞肥大及肌球蛋白重链基因表达的影响[J].临床心血管病杂志,2002,18(4)：171-172.
[113]胡迎春,欧阳静萍,李艳琴,等.苦参碱对醛固酮诱导大鼠心肌成纤维细胞细胞周期和增殖细胞核抗原表达的影响[J].武汉大学学报(医学版),2004,25(3)：224.
[114]陆泽安,李庆平,饶曼人,等.粉防已碱对高血压心肌肥厚大鼠心肌胶原含量和肌球蛋白ATP酶活性影响[J].中国药理学与毒理学杂志,2001,15(2)：121-124.
[115]RAO Man-Ren. Effects of tetrandrine on cardiac and vascular remodeling [J]. Acta Pharmacol Sin,2002,23(12):1075-1085.
[116]Rang WQ, Du YH, Hu CP, et al. Protective effects of evodiamine on myocardial ischemia-reperfusion injury in rats[J]. Planta Med,2004,70 (12):1140-1143.
[117]郑敏,吴基良,李立中,等.牛磺酸对肾性高血压大鼠血浆及心肌血管紧张素Ⅱ、醛固酮的影响[J].中国心血管杂志,2003,8(5)：313-315.
[118]黄荣杰,刘唐威,庞玉生.牛磺酸对扩张心肌病大鼠左心室肌转化生长因子p1表达的影响[J].现代诊断与治疗,2004,15(2)：83-85.
[119]阿魏酸钠对心肌细胞缺氧／复氧损伤的保护作用及其机制.药学学报,2004,39(5)：325-327.
[120]李屏,曾秋棠,周彤,等.阿魏酸钠抗心律失常机制的初步探讨.贵州医药,2001,,25(10)：884-886.
[121]Geiger B, Ayalon O. Cadherins [J]. Annu Rev Cell Biol,1992,8:307-332.
[122]Juliano RL, Haskell S. Signal transduction from the extracellular matrix [J]. J Cell Biol,1993,120:577-585.
[123]Perriard JC, Hirschy A, Ehler E. Dilated cardiomyopathy:a disease of the intercalated disc [J]? Trends Cardiovasc Med,2003,13:30-38.
[124]Pellieux C, Foletti A, Peduto G, et al. Dilated cardiomyopathy and impaired cardiac hypertrophic response to angiotensin II in mice lacking FGF-2 [J]. J Clin Invest,2001,108:1843-1851.
[125]Zhang H, Sunnarborg SW, Faber JE. Heparin-Binding EGF-Like Growth Factor (HB-EGF) mediates low flow-induced negative hypertrophic remodeling (FINR) but not high flow-induced positive eutrophic remodeling (FIPR) of carotid artery [J]. Circulation,2006,114:217-223.
[126]Erin E, Tansey BS, Kevin F, et al. Reduction and redistribution of gap and adherens junction proteins after ischemia and reperfusion [J]. Ann Thorac Surg,2006, 82(4):1472-1479.
[127]Hagendorff A, Schumacher B, Kirchhoff S, et al. Conduction disturbances and increased atrial vulnerability in connexin 40 deficent mice analyzed by transesophyageal stimulation [J]. Circulation,1999,99:1508-1515.
[128]Ferreira-Cornwell MC, Luo Y, Narula N, et al. Remodeling the intercalated disc leads to cardiomyopathy in mice misexpressing cadherins in the heart [J]. J Cell Sci, 2002,115:1623-1634.
[129]Brancaccio M, Hirsch E, Notte A, et al. Integrin signalling:the tug-of-war in heart hypertrophy [J]. Cardiovasc Res,2006,70:422-433.
[130]Srivastava D, Yu S. Stretching to meet needs:integrin-linked kinase and the cardiac pump [J]. Genes Dev,2006,20:2361-72.
[131]Bouzeghrane F, Mercure C, Reudelhuber TL, et al. Alpha8betal integrin is upregulated in myofibroblasts of fibrotic and scarring myocardium [J]. J Mol Cell Cardiol,2004,36:343-353.
[132]Li J, Mayne R, Wu C. A novel muscle-specific β1 integrin binding protein (MIBP) that modulates myogenic differentiation [J]. J Cell Biol,1999,147:1391-1398.
[133]Nojiri H, Shimizu T, Funakoshi M, et al. Oxidative stress causes heart failure with impaired mitochondrial respiration [J]. J Biol Chem,2006,281:33789-33801.
[134]Lu QW, Morimoto S, Harada K, et al. Cardiac troponin T mutation R141W found in dilated cardiomyopathy stabilizes the troponin T-tropomyosin interaction and causes a Ca2+ desensitization [J]. J Mol Cell Cardiol,2003,35:1421-1427.
[135]Valencik ML, Zhang DF, Punske B, et al. Integrin activation in the heart:a link between electrical and contractile dysfunction [J]? Circ Res,2006,99:1403-1410.
[136]付金容,唐其柱,沈涤非,等.整合素β1在自身免疫性心肌炎小鼠心肌的表达[J].心脏杂志,2005,17(1)：25-28.
[137]Fujino T, Hasebe N, Fujita M, et al. Enhanced expression of heparin-binding EGF-like growth factor and its receptor in hypertrophied left ventricle of spontaneously hypertensive rats [J]. Cardiovasc Res,1998,38:365-374.
[138]Iwabu A, Murakami T, Kusachi S, et al. Concomitant expression of heparin-binding epidermal growth factor-like growth factor mRNA and basic fibroblast growth factor mRNA in myocardial infarction in rats [J]. Basic Res Cardiol, 2002,97:214-222.
[139]Ushikoshi H, Takahashi T, Chen XH, et al. Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes [J]. Lab Invest,2005,85:862-873.
[140]Yoshioka J, Prince RN, Huang H, et al. Cardiomyocyte hypertrophy and degradation of connexin43 through spatially restricted autocrine/paracrine heparin-binding EGF [J]. PNAS,2005,102:10622-10627.
[141]Asakura M, Kitakaze M, Takashima S, et al. Cardiac hypertrophy is inhibited by antagonism of ADAM 12 processing of HB-EGF:metalloproteinase inhibitors as a new therapy [J]. Nature Med,2002,8:35-40.
[142]Lee KS, Park JH, Lee S, et al. HB-EGF induces delayed STAT3 activation via NF-kappaB mediated IL-6 secretion in vascular smooth muscle cell [J]. Biochim Biophys Acta,2007,1773:1637-44.
[143]Ng DC, Court NW, dos Remedios CG, et al. Activation of signal transducer and activator of transcription (STAT) pathways in failing human hearts [J]. Cardiovasc Res,2003,57:333-346.
[144]Sun LG, Ma KW, Wang HX, et al. JAK1-STAT1-STAT3, a key pathway promoting proliferation and preventing premature differentiation of myoblasts [J]. J Cell Biol,2007,179:129-138.
[145]Yamauchi-Takihara K, Kishimoto T. A novel role for STAT3 in cardiac remodeling [J]. Trends Cardiovasc Med,2000,10:298-303.
[146]Yamauchi-Takihara K, Kishimoto T. Cytokines and their receptors in cardiovascular diseases-role of gp130 signaling pathway in cardiac myocyte growth and maintenance [J]. Int J Exp Pathol,2000,81:1-16.
[147]Kunisada K, Negoro S, Tone E, et al. Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin-induced cardiomyopathy [J]. PNAS,2000,97:315-319.
[148]Negoro S, Kunisada K, Fujio Y, et al. Activation of signal transducer and activator of transcription 3 protects cardiomyocytes from hypoxia/ reoxygenation-induced oxidative stress through the upregulation of manganese superoxide dismutase [J]. Circulation,2001,104:979-981.
[149]Ku L, Feiger L, Taylor M, et al. Familial dilated cardiomyopathy [J]. Circulation, 2003,108:e118-e121.
[150]O'Connell JB, Moore CK, Waterer HC. Treatment of end stage dilated cardiomyopathy [J]. Br Heart J,1994,72 (Supplement):S 52-S 56.Massin EK. Current treatment of dilated cardiomyopathy [J]. Texas Heart Institute Journal,1991, 18:41-49.
[151]Attele AS, Wu JA, Yuan CS, et al. Ginseng pharmacology:multiple constituents and multiple actions [J]. Biochem Pharmacol,1999,58:1685-1693.
1.邓江,吴芹,黄燮南.川芎嗪对大鼠压力超负荷心肌细胞外信号调节激酶1mRNA表达的抑制作用.中国药理学与毒理学杂志,2008,22：336-340.
2.蒋青松，黄燮南,戴支凯,等.川芎嗪对PGF2α诱导心肌肥大的抑制作用.中药药理与临床,2005,21：9-11.
3.任海玲,江时森,谢渡江,等.中药川芎嗪对慢性压力超负荷大鼠心肌纤维化的干预作用[J].中国临床康复,2003,7(12)：1748-1749.
4.宋德明,苏海,吴美华,等.川芎嗪、丹参对心肌成纤维细胞胶原合成和细胞增殖的影响[J].中国中西医结合杂志,1998,18(7)：423-425.
5.郭自强,牛福玲.川芎嗪对血管紧张素Ⅱ致心肌肥大的影响[J].北京中医药大学学报,2001,24(3)：32-34.
6.张冬梅,秦英,杨君,等.川芎嗪对血管紧张素Ⅱ诱导的人al(Ⅰ)胶原基因启动子活性的影响[J].中国中医药信息杂志,2005,12(9)：21-22.
7. 王振涛,韩丽华,朱明军,等.川芎嗪注射液促心梗后大鼠缺血心肌血管新生作用及相关生长因子影响的研究[J].辽宁中医杂志,2006,33(7)：888-890.
8.余乐涵,赵小曼,李华,等。川芎嗪对缺血再灌注后心肌细胞凋亡的影响[J].江西医学院学报,2006,46(3)：27-29.
9. Hintz KK, Ren J (2003). Tetramethylpyrazine elicits disparate responses in cardiac contraction and intracellular Ca(2+) transients in isolated adult rat ventricular myocytes. Vascular Pharmacology 40:213-217.
10. Sheu JR, Kan YC, Hung WC, Lin CH, Yen MH (2000). The antiplatelet activity of tetramethylpyrazine is mediated through activation of NO synthase. Life Sci 67: 937-947.
11. Lin CI, Wu SL, Tao PL, Chen HM, Wei J (1993). The role of cyclic AMP and phosphodiesterase activity in the mechanism of action of tetramethylpyrazine on human and dog cardiac and dog coronary arterial tissues. J Pharm Pharmacol 45: 963-966.
12. Shih YH, Wu SL, Chiou WF, Ku HH, Ko TL, Fu YS (2002). Protective effects of tetramethylpyrazine on kainate-induced excitotoxicity in hippocampal culture. Neuroreport 13:515-519.
13. Zhang Z, Wei T, Hou J, Li G, Yu S, Xin W (2003). Tetramethylpyrazine scavenges superoxide anion and decreases nitric oxide production in human polymorphonuclear leukocytes. Life Sci 72:2465-2472.
14. Sutter MC, Wang YX. (1993). Recent cardiovascular drugs from Chinese medicinal plants. Cardiovasc Res 27:1891-1901.
15. Zhang ZH, Yu SZ, Wang ZT, Zhao BL, Hou JW, Yang FJ, et al. (1994). Scavenging effects of tetramethylpyrazine on active oxygen free radicals. Acta Pharmacol Sin 5: 229-231.
16.赵玉清,笔雪艳.磷酸川芎嗪注射液药理毒理研究综述.时珍国医国药.2007,7.
17. Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure[J]. Eur Heart J,2001,22,1527-1560.
18.黄斌.扩张性心肌病患者血浆BNP水平与左心功能关系的研究.临床医学工程,2008,5：9.
19. Rupp H, Jacob R. Myocardial transitions between fast-and slow-type muscle as monitored by the population of myosin isoenzymes [A]. In:Rupp H, ed. Regulation of heart function [M]. New York:Thieme Inc.,1986:271-291.
20. Salmikangas P, van der Ven PF, Lalowski M, Taivainen A, Zhao F, Suila H, et al. (2003). Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly. Hum Mol Genet 12: 189-203.
21. Zeller R, Ivandic BT, Ehlermann P, Mucke O, Zugck C, Remppis A, et al. (2006). Large-scale mutation screening in patients with dilated or hypertrophic cardiomyopathy:a pilot study using DGGE. J Mol Med 84:682-691.
22. Hauser MA, Horrigan SK, Salmikangas P, Torian UM, Viles KD, Dancel R, et al. (2000). Myotilin is mutated in limb girdle muscular dystrophy 1A. Hum Mol Genet 9: 2141-2147.
23. Hauser MA, Conde CB, Kowaljow V, Zeppa G, Taratuto AL, Torian UM, et al. (2002). Myotilin mutation found in second pedigree with LGMD1A. Am J Hum Genet,71,1428-1482.
24. Garvey SM, Liu Y, Miller SE, Hauser MA (2008). Myotilin overexpression enhances myopathology in the LGMD1A mouse model. Muscle Nerve 37:663-7.
25. Moza M, Mologni L, Trokovic R, Faulkner G, Partanen J, Carpen O (2007). Targeted Deletion of the Muscular Dystrophy Gene myotilin Does Not Perturb Muscle Structure or Function in Mice. Mol Cell Biol.27:244-252.
26. Flavigny J, Richard P, Isnard R, Carrier L, Charron P, Bonne G et al., (1998). Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy. J Mol Med 76:208-214.
27. Margossian SS, White HD, Caulfield JB, Norton P, Taylor S, Slayter HS (1992). Light chain 2 profile and activity of human ventricular myosin during dilated cardiomyopathy. Identification of a causal agent for impaired myocardial function. Circulation 85:1720-1733.
28. Corbett JM, Why HJ, Wheeler CH, Richardson PJ, Archard LC, Yacoub MH et al. (1998). Cardiac protein abnormalities in dilated cardiomyopathy detected by two-dimensional polyacrylamide gel electrophoresis. Electrophoresis 19:2031-2042.
29. Chen J, Kubalak SW, Minamisawa S, Price RL, Becker KD, Hickey R et al. (1998). Selective requirement of myosin light chain 2v in embryonic heart function. J Biol Chem 273:1252-1256.
30. Morano I. Tuning the human heart molecular motors by myosin light chains. J Mol Med 1999,77:544-555.
31. Davis JS, Hassanzadeh S, Winitsky S, Lin H, Satorius C, Vemuri R, et al. The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation. Cell,2001,107:631641.
32. Morano I. Effects of different expression and posttranslational modifications of myosin light chains on contractility of skinned human cardiac fibers. Basic Res Cardiol,1992,87:129-141.
33. Sanbe A, Fewell JG, Gulick J, Osinska H, Lorenz J, Hall DG, et al. Abnormal Cardiac Structure and Function in Mice Expressing Nonphosphorylatable Cardiac Regulatory Myosin Light Chain 2. J Biol Chem,1999,274:21085-21094.
34. Zhang T and Brown JH. Role of Ca2+/calmodulin-dependent protein kinase Ⅱ in cardiac hypertrophy and heart failure, Cardiovasc Res,2004,63:476-486.
35. Zhang R, Khoo MS, Wu Y, Yang Y, Grueter CE, Ni G et al. Calmodulin kinase Ⅱ inhibition protects against structural heart disease, Nat Med,2005,11:409-417.
[1]Koseki T, Inohara N, Chen S, et al. ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases [J].Proc Natl Acad Sci USA,1998,95(9):5156-5160.
[2]Geertman R, McMahon A, Sabban EL. Cloning and characterization of cDNAs for novel proteins with glutamic acidproline dipeptide tandem repeats[J]. Biochim Biophys Acta,1996,1306:147-152.
[3]Abmayr S, Crawford RW, Chamberlain JS. Characterization of ARC, apoptosis repressor interacting with CARD, in normal and dystrophin—deficient skeletal muscle[J]. Hum Mol Genet,2004,13:213—221.
[4]Donath S, Li PF, Willenbockel C, et al. Apoptosis repressor with caspase recruitment domain is required for cardioprotection in response to biomechanical and ischemic stress[J]. Circulation,2006,113:1203-1212.
[5]Gustafsson AB, Sayen MR, Williams SD, et al. TAT protein transduction into isolated perfused hearts, TAT-apoptosis repressor with caspase recruitment domain is cardioprotective[J]. Circulation,2002,106:735-739.
[6]Yaniv G, Shilkrut M, Larisch S, et al. Hydrogen peroxide predisposes neonatal rat ventricular myocytes to Fas-mediated apoptosis[J]. Biochem Biophys Res Commun, 2005,336(3):740-746.
[7]Ekhterae D, Lin Z, Lundberg MS, et al. ARC inhibits cytochrome c release from mitochondria and protects against hypoxia-induced apoptosis in heart-derived H9c2 cells[J]. Circ Res,1999,85(12):e70-77.
[8]Neuss M, Monticone R, Lundberg MS, et al. The apoptotic regulatory protein ARC (apoptosis repressor with caspase recruitment domain) prevents oxidant stress-mediated cell death by preserving mitochondrial function[J]. J Biol Chem,2001, 276 (36):33915-33922.
[9]Nam Y J, Mani K, Ashton AW, et al. Inhibition of both the extrinsic and intrinsic death pathways through nonhomotypic death-fold interactions [J]. Mol Cell,2004, 15(6):901-912.
[10]李玉珍.心脏特异性高度表达的抗凋亡蛋白—ARC[J].生物化学与生物物理进展.2006,33(9)：816-819.
[11]Gustafsson AB, Tsai JG, Logue SE, et al. Apoptosis repressor with caspase recruitment domain protects against cell death by interfering with Bax activation[J]. J Biol Chem,2004,279(20):21233-21238.
[12]Jo DG, Jun JI, Chang JW, et al. Calcium binding of ARC mediates regulation of caspase 8 and cell death[J]. Mol Cell Biology,2004,24 (22):9763-9769.
[13]Ekhterae D, Platoshyn O, Zhang S, et al. Apoptosis repressor with caspase domain inhibits cardiomyocyte apoptosis by reducing K+currents[J]. Am J Physiol Cell Physiol,2003,284:1405-1410.