芪苈强心胶囊治疗慢性心力衰竭作用机制研究进展
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摘要
慢性心力衰竭(慢性心衰)是心血管事件链中的关键环节,以中医脉络学说为指导研发的创新中药芪苈强心胶囊对慢性心衰具有良好疗效,研究表明该药能够增强心肌收缩力,利尿,抑制神经内分泌系统过度激活,抑制炎症反应、心肌纤维化、细胞凋亡和自噬,改善心肌能量代谢,促进血管新生,改善内皮功能,从而抑制心室重构,延缓慢性心衰进程。探讨芪苈强心胶囊治疗慢性心衰的作用及机制,有利于从多靶点、多通道发挥该药治疗作用,同时为心血管事件链中其他难治性疾病提供更广阔的治疗思路,对提高中医药治疗心血管疾病具有重大的理论与临床意义。
Chronic heart failure is a key part of cardiovascular continuum. Under the guidance of the theory of vessel-collateral doctrine,the present study proposes therapeutic benefits of Qili Qiangxin Capsules,an innovative Chinese medicine,on chronic heart failure. The studies show that multiple targets of the drug on chronic heart failure,including enhancing myocardial systole,promoting urine excretion,inhibiting excessive activation of the neuroendocrine system,preventing ventricular remodeling by inhibiting inflammatory response,myocardial fibrosis,apoptosis and autophagy,enhancing myocardial energy metabolism,promoting angiogenesis and improving endothelial function. To investigate the effect and mechanism of the drug is beneficial to the treatment of chronic heart failure through multiple targets or signaling pathways. Meanwhile,it provides new insights to further understand other refractory diseases in the cardiovascular continuum,and it also has an important theoretical and practical significance in enhancing prevention and therapeutic effect of traditional Chinese medicine for these diseases.
Chronic heart failure is a key part of cardiovascular continuum. Under the guidance of the theory of vessel-collateral doctrine,the present study proposes therapeutic benefits of Qili Qiangxin Capsules,an innovative Chinese medicine,on chronic heart failure. The studies show that multiple targets of the drug on chronic heart failure,including enhancing myocardial systole,promoting urine excretion,inhibiting excessive activation of the neuroendocrine system,preventing ventricular remodeling by inhibiting inflammatory response,myocardial fibrosis,apoptosis and autophagy,enhancing myocardial energy metabolism,promoting angiogenesis and improving endothelial function. To investigate the effect and mechanism of the drug is beneficial to the treatment of chronic heart failure through multiple targets or signaling pathways. Meanwhile,it provides new insights to further understand other refractory diseases in the cardiovascular continuum,and it also has an important theoretical and practical significance in enhancing prevention and therapeutic effect of traditional Chinese medicine for these diseases.
引文
[1]黄峻,马长生,郭继鸿,等.心血管内科学高级教程[M].北京:人民军医出版社,2013:166-167.
[2]林曙光.当代心血管学进展[M].北京:人民军医出版社,2009:99.
[3]Yancy CW,Jessup M,Bozkurt B,et al.2017 ACC/AHA/HFSAFocused Update of the 2013 ACCF/AHA Guideline for the management of heart failure:a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the heart failure society of America[J].J Am Coll Cardiol,2017,70(6):776-803.
[4]吴以岭.脉络论[M].北京:中国科学技术出版社,2010:1302.
[5]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.中国心力衰竭诊断和治疗指南2014[J].中华心血管病杂志,2014,42(2):98-122.
[6]Jin S,Kang Zh,Wen JX,et al.Clinical effects of a standardized Chinese herbal remedy,Qiliqiangxin,as an adjuvant treatment in heart failure:systematic review and meta-analysis[J].BMC Complementary and Alternative Medicine,2016,16:201.
[7]Li XL,Zhang J,Huang J,et al.A multicenter,randomized,doubleblind,parallel-group,placebo controlled study of the effects of qiliqiangxin capsules in patients with chronic heart failure[J].J Am Coll Cardiol.2013,62,1065-1072.
[8]刘树峰,严晓红,肖敦宏,等.芪苈强心胶囊辅治慢性心力衰竭患者的疗效及其对NT-proBNP、LVEF及Tei指数的影响[J].疑难病杂志,2017,16(5):505-508.
[9]向常清,贺海波,周敬群,等.芪苈强心胶囊对慢性收缩性心力衰竭患者血清可溶性ST2的影响[J].现代中西医结合杂志,2018,27(2):147-153.
[10]陈枫,李玉英,黄云剑,等.芪苈强心胶囊改善维持性血液透析患者尿毒症性心肌病的临床观察[J].解放军医药杂志,2016,28(6):8-10.
[11]李琳,李琦,王金会,等.芪苈强心胶囊相关地高辛浓度监测165例分析[J].中医药导报,2016,22(1):82-84.
[12]杨安仲.芪苈强心胶囊治疗慢性肺心病难治性心力衰竭临床观察[J].中国实用内科杂志,2016,36(1):26-28.
[13]Jung HJ,Kwon TH.Molecular mechanisms regulating aquaporin-2in kidney collecting duct[J].Am J Physiol Renal Physiol,2016,311:1318-1328.
[14]邬真力,许顶立,林昇,等.芪苈强心胶囊对慢性心力衰竭大鼠心脏功能及血浆血管加压素的影响[J].疑难病杂志,2011,10(2):120-122.
[15]张健,崔向宁,曹戬.芪苈强心胶囊对改善慢性心力衰竭大鼠心功能及AQP-2表达的影响[J].中国实验方剂学杂志,2014,20(10):183-187.
[16]马柳一,尹玉洁,张军芳,等.芪苈强心胶囊对慢性心衰大鼠下丘脑室旁核RAS系统及交感神经系统的影响[J].中国药理学通报,2016,32(4):575-80.
[17]Mouton AJ,Rivera Gonzalez OJ,Lindsey ML,et al.Myocardial infarction remodeling that progresses to heart failure:a signaling misunderstanding[J].Am J Physiol Heart Circ Physiol,2018,Mar 30.
[18]Huang S,Frangogiannis NG.Anti-inflammatory therapies in myocardial infarction:failures,hopes and challenges[J].Br J Pharmacol,2018,Feb 2.
[19]Han A,Lu Y,Zheng Q,et al.Qiliqiangxin attenuates cardiac remodeling via inhibition of TGF-β1/Smad3 and NF-κB signaling pathways in a rat model of myocardial infarction[J].Cell Physiol Biochem,2018,45(5):1797-1806.
[20]秘红英,常丽萍,郎艳松,等.芪苈强心胶囊对慢性心衰大鼠下丘脑细胞炎性因子的影响[J].中国新药杂志,2015,24(8):924-929.
[21]Curley D,Lavin Plaza B,Shah AM,et al.Molecular imaging of cardiac remodeling after myocardial infarction[J].Basic Res Cardiol,2018,113(2):10.
[22]李娅,宋优,程翔,等.芪苈强心胶囊对大鼠心肌梗死后心肌重构及心功能的影响[J].中国分子心脏病学杂志,2007,7(4):201-204.
[23]Shen S,Jiang H,Bei Y,et al.Qiliqiangxin attenuates adverse cardiac remodeling after myocardial infarction in ovariectomized mice via activation of PPARγ[J].Cell Physiol Biochem,2017,42(3):876-888.
[24]Zhou J,Jiang K,Ding X,et al.Qiliqiangxin inhibits angiotensin II-induced transdifferentiation of rat cardiac fibroblasts through suppressing interleukin-6[J].J Cell Mol Med,2015,19(5):1114-21.
[25]Zhang J,Huang M,Shen S,et al.,Qiliqiangxin attenuates isoproterenol-induced cardiac remodeling in mice[J].Am J Transl Res,2017 Dec.
[26]Wang H,Zhang X,Yu P,et al.Traditional Chinese medication qiliqiangxin protects against cardiac remodeling and dysfunction in spontaneously hypertensive rats[J].Int J Med Sci,2017,14(5):506-514.
[27]Ye Y,Gong H,Wang X,et al.Combination treatment with antihypertensive agents enhances the effect of Qiliqiangxin on chronic pressure overload-induced cardiac hypertrophy and remodeling in Male Mice[J].J Cardiovasc Pharmacol,2015,65(6):628-39.
[28]Zou Y,Lin L,Ye Y,et al.Qiliqiangxin inhibits the development of cardiac hypertrophy,remodeling,and dysfunction during 4 weeks of pressure overload in mice[J].J Cardiovasc Pharmacol,2012,59(3):268-80.
[29]Angelini A,Pi X,Xie L.Dioxygen and metabolism;dangerous liaisons in cardiac function and disease[J].Front Physiol,2017,8:1044.
[30]Carpentier AC.Abnormal myocardial dietary fatty acid metabolism and diabetic cardiomyopathy[J].Can J Cardiol,2018 Jan 16.
[31]Warda M,Kim HK,Kim N,et al.A matter of life,death and diseases:Mitochondria from a proteomic perspective[J].Expert Rev Proteomics,2013,10:97-111.
[32]Lin S,Wu X,Tao L,et al.The metabolic effects of traditional Chinese medication Qiliqiang xin on H9c2 cardiomyocytes[J].Cell Physiol Biochem.2015;37(6):2246-56.
[33]Wang Y,Han X,Fu M,et al.Qiliqiangxin attenuates hypoxiainduced injury in primary rat cardiac microvascular endothelial cells via promoting HIF-1α-dependent glycolysis[J].J Cell Mol Med,2018 Mar 4.
[34]常丽萍,秘红英,张军芳,等.芪苈强心胶囊对AMI致CHF大鼠脂肪酸代谢的影响[J].中国中西医结合杂志,2017,37(6):716-720.
[35]Tocchetti CG,Gallucci G,Coppola C,et al.The emerging issue of cardiac dysfunction induced by antineoplastic angiogenesis inhibitors[J].Eur J Heart Fail,2013,15(5):482-489.
[36]Wang J,Zhou J,Wang Y,et al.Qiliqiangxin protects against anoxic injury in cardiac microvascular endothelial cells via NRG-1/ErbB-PI3K/Akt/mTOR pathway[J].J Cell Mol Med,2017,21(9):1905-1914.
[37]Liang T,Zhang Y,Yin S,et al.Cardio-protect effect of qiliqiangxin capsule on left ventricular remodeling,dysfunction and apoptosis in heart failure rats after chronic myocardial infarction[J].Am J Transl Res,2016,8(5):2047-58.
[38]常成成,位庚,李红蓉,等.微血管内皮细胞损伤在心血管疾病发病中的作用及通络干预研究进展[J].时珍国医国药,2015,26(6):1459-1462.
[39]陈亚青,刘丹,陈亚静,等.芪苈强心胶囊联合通心络胶囊治疗扩张型心肌病心衰疗效观察[J].中西医结合心脑血管病杂志,2017,15(3):332-335.
[40]吴相君,赵保礼,韩硕龙,等.芪苈强心胶囊对扩张型心肌病患者心功能及血管内皮功能影响的临床研究[J].疑难病杂志,2018,17(4):329-333.
[2]林曙光.当代心血管学进展[M].北京:人民军医出版社,2009:99.
[3]Yancy CW,Jessup M,Bozkurt B,et al.2017 ACC/AHA/HFSAFocused Update of the 2013 ACCF/AHA Guideline for the management of heart failure:a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the heart failure society of America[J].J Am Coll Cardiol,2017,70(6):776-803.
[4]吴以岭.脉络论[M].北京:中国科学技术出版社,2010:1302.
[5]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.中国心力衰竭诊断和治疗指南2014[J].中华心血管病杂志,2014,42(2):98-122.
[6]Jin S,Kang Zh,Wen JX,et al.Clinical effects of a standardized Chinese herbal remedy,Qiliqiangxin,as an adjuvant treatment in heart failure:systematic review and meta-analysis[J].BMC Complementary and Alternative Medicine,2016,16:201.
[7]Li XL,Zhang J,Huang J,et al.A multicenter,randomized,doubleblind,parallel-group,placebo controlled study of the effects of qiliqiangxin capsules in patients with chronic heart failure[J].J Am Coll Cardiol.2013,62,1065-1072.
[8]刘树峰,严晓红,肖敦宏,等.芪苈强心胶囊辅治慢性心力衰竭患者的疗效及其对NT-proBNP、LVEF及Tei指数的影响[J].疑难病杂志,2017,16(5):505-508.
[9]向常清,贺海波,周敬群,等.芪苈强心胶囊对慢性收缩性心力衰竭患者血清可溶性ST2的影响[J].现代中西医结合杂志,2018,27(2):147-153.
[10]陈枫,李玉英,黄云剑,等.芪苈强心胶囊改善维持性血液透析患者尿毒症性心肌病的临床观察[J].解放军医药杂志,2016,28(6):8-10.
[11]李琳,李琦,王金会,等.芪苈强心胶囊相关地高辛浓度监测165例分析[J].中医药导报,2016,22(1):82-84.
[12]杨安仲.芪苈强心胶囊治疗慢性肺心病难治性心力衰竭临床观察[J].中国实用内科杂志,2016,36(1):26-28.
[13]Jung HJ,Kwon TH.Molecular mechanisms regulating aquaporin-2in kidney collecting duct[J].Am J Physiol Renal Physiol,2016,311:1318-1328.
[14]邬真力,许顶立,林昇,等.芪苈强心胶囊对慢性心力衰竭大鼠心脏功能及血浆血管加压素的影响[J].疑难病杂志,2011,10(2):120-122.
[15]张健,崔向宁,曹戬.芪苈强心胶囊对改善慢性心力衰竭大鼠心功能及AQP-2表达的影响[J].中国实验方剂学杂志,2014,20(10):183-187.
[16]马柳一,尹玉洁,张军芳,等.芪苈强心胶囊对慢性心衰大鼠下丘脑室旁核RAS系统及交感神经系统的影响[J].中国药理学通报,2016,32(4):575-80.
[17]Mouton AJ,Rivera Gonzalez OJ,Lindsey ML,et al.Myocardial infarction remodeling that progresses to heart failure:a signaling misunderstanding[J].Am J Physiol Heart Circ Physiol,2018,Mar 30.
[18]Huang S,Frangogiannis NG.Anti-inflammatory therapies in myocardial infarction:failures,hopes and challenges[J].Br J Pharmacol,2018,Feb 2.
[19]Han A,Lu Y,Zheng Q,et al.Qiliqiangxin attenuates cardiac remodeling via inhibition of TGF-β1/Smad3 and NF-κB signaling pathways in a rat model of myocardial infarction[J].Cell Physiol Biochem,2018,45(5):1797-1806.
[20]秘红英,常丽萍,郎艳松,等.芪苈强心胶囊对慢性心衰大鼠下丘脑细胞炎性因子的影响[J].中国新药杂志,2015,24(8):924-929.
[21]Curley D,Lavin Plaza B,Shah AM,et al.Molecular imaging of cardiac remodeling after myocardial infarction[J].Basic Res Cardiol,2018,113(2):10.
[22]李娅,宋优,程翔,等.芪苈强心胶囊对大鼠心肌梗死后心肌重构及心功能的影响[J].中国分子心脏病学杂志,2007,7(4):201-204.
[23]Shen S,Jiang H,Bei Y,et al.Qiliqiangxin attenuates adverse cardiac remodeling after myocardial infarction in ovariectomized mice via activation of PPARγ[J].Cell Physiol Biochem,2017,42(3):876-888.
[24]Zhou J,Jiang K,Ding X,et al.Qiliqiangxin inhibits angiotensin II-induced transdifferentiation of rat cardiac fibroblasts through suppressing interleukin-6[J].J Cell Mol Med,2015,19(5):1114-21.
[25]Zhang J,Huang M,Shen S,et al.,Qiliqiangxin attenuates isoproterenol-induced cardiac remodeling in mice[J].Am J Transl Res,2017 Dec.
[26]Wang H,Zhang X,Yu P,et al.Traditional Chinese medication qiliqiangxin protects against cardiac remodeling and dysfunction in spontaneously hypertensive rats[J].Int J Med Sci,2017,14(5):506-514.
[27]Ye Y,Gong H,Wang X,et al.Combination treatment with antihypertensive agents enhances the effect of Qiliqiangxin on chronic pressure overload-induced cardiac hypertrophy and remodeling in Male Mice[J].J Cardiovasc Pharmacol,2015,65(6):628-39.
[28]Zou Y,Lin L,Ye Y,et al.Qiliqiangxin inhibits the development of cardiac hypertrophy,remodeling,and dysfunction during 4 weeks of pressure overload in mice[J].J Cardiovasc Pharmacol,2012,59(3):268-80.
[29]Angelini A,Pi X,Xie L.Dioxygen and metabolism;dangerous liaisons in cardiac function and disease[J].Front Physiol,2017,8:1044.
[30]Carpentier AC.Abnormal myocardial dietary fatty acid metabolism and diabetic cardiomyopathy[J].Can J Cardiol,2018 Jan 16.
[31]Warda M,Kim HK,Kim N,et al.A matter of life,death and diseases:Mitochondria from a proteomic perspective[J].Expert Rev Proteomics,2013,10:97-111.
[32]Lin S,Wu X,Tao L,et al.The metabolic effects of traditional Chinese medication Qiliqiang xin on H9c2 cardiomyocytes[J].Cell Physiol Biochem.2015;37(6):2246-56.
[33]Wang Y,Han X,Fu M,et al.Qiliqiangxin attenuates hypoxiainduced injury in primary rat cardiac microvascular endothelial cells via promoting HIF-1α-dependent glycolysis[J].J Cell Mol Med,2018 Mar 4.
[34]常丽萍,秘红英,张军芳,等.芪苈强心胶囊对AMI致CHF大鼠脂肪酸代谢的影响[J].中国中西医结合杂志,2017,37(6):716-720.
[35]Tocchetti CG,Gallucci G,Coppola C,et al.The emerging issue of cardiac dysfunction induced by antineoplastic angiogenesis inhibitors[J].Eur J Heart Fail,2013,15(5):482-489.
[36]Wang J,Zhou J,Wang Y,et al.Qiliqiangxin protects against anoxic injury in cardiac microvascular endothelial cells via NRG-1/ErbB-PI3K/Akt/mTOR pathway[J].J Cell Mol Med,2017,21(9):1905-1914.
[37]Liang T,Zhang Y,Yin S,et al.Cardio-protect effect of qiliqiangxin capsule on left ventricular remodeling,dysfunction and apoptosis in heart failure rats after chronic myocardial infarction[J].Am J Transl Res,2016,8(5):2047-58.
[38]常成成,位庚,李红蓉,等.微血管内皮细胞损伤在心血管疾病发病中的作用及通络干预研究进展[J].时珍国医国药,2015,26(6):1459-1462.
[39]陈亚青,刘丹,陈亚静,等.芪苈强心胶囊联合通心络胶囊治疗扩张型心肌病心衰疗效观察[J].中西医结合心脑血管病杂志,2017,15(3):332-335.
[40]吴相君,赵保礼,韩硕龙,等.芪苈强心胶囊对扩张型心肌病患者心功能及血管内皮功能影响的临床研究[J].疑难病杂志,2018,17(4):329-333.
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