基于慢性心衰大鼠模型的附子汤药效学作用评价及机制探讨
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摘要
研究首先建立慢性心力衰竭大鼠模型,观察不同提取方法及不同给药剂量附子汤对模型大鼠的疗效并探讨其作用机制。122只SD大鼠雌雄各半,采用腹主动脉缩窄法制作心力衰竭大鼠模型,手术8周后以左室舒张末期内径(LVIDd)、左室收缩末期内径(LVIDs)、左室射血分数(LVEF)、左室短轴缩短率(FS)、心电图和血清中BNP表达为慢性心力衰竭指标,造模成功后随机分为假手术组,模型组,附子汤水煎液高剂量组,附子汤70%乙醇总提物低、中、高剂量组,阳性药卡托普利组。给药4周,取血清进行ELISA检测。附子汤70%乙醇总提物可明显降低慢性心衰大鼠BNP、NT-proBNP、IL-6、TNF-α、Ang-II、ALD、CK、ET-1、LDH、PRA、CRP的含量。70%乙醇总提物中、高剂量组对于慢性心衰大鼠心功能的改善显著优于附子汤水煎液高剂量组;附子汤通过抑制肾素-血管生成素-醛固酮系统(RAAS)的活性,下调慢性心衰大鼠神经细胞因子的含量,调节神经内分泌,改善心室重构,从而改善心功能、减轻心衰症状。
It is to investigate the protective effects and mechanism of Fuzi Decoction with different extraction methods and different dosages on chronic heart failure rats. Chronic heart failure rats were induced by constricting the abdominal aorta. In this experiment, left ventricular end diastolic diameter(LVIDd), left ventricular end systolic diameter(LVIDs), left ventricular ejection fraction(LVEF), fractional shortening(FS), electrocardiogram and Expression of BNP in serum were used as indexes of chronic heart failure after 8 weeks of operation. After successful modeling, 122 SD rats were randomly divided into sham operation group, model group, high dose group of Fuzi Decoction extracted by water, low, medium and high groups of Fuzi Decoction extracted by 70% ethanol and Captopril group. After 4 weeks of administration, the serum was detected by ELISA. Fuzi Decoction extracted by 70% ethanol could significantly reduce the contents of BNP, NT-proBNP, IL-6, TNF-α, Ang-II, ALD, CK, ET-1, LDH, PRA and CRP in chronic heart failure rats. In the process of cardiac function improvement in chronic heart failure rats, the alcohol extracts in the middle and high dose groups were more effective than tthose of the large doses of water extract. Fuzi Decoction can down-regulate the content of nerve cell factor in chronic heart failure rats by inhibiting activity the renin aldosterone system of angiogenin(RAAS) and regulate nerve endocrine, improve ventricular remodeling and heart function, reduce the symptoms of heart failure.
It is to investigate the protective effects and mechanism of Fuzi Decoction with different extraction methods and different dosages on chronic heart failure rats. Chronic heart failure rats were induced by constricting the abdominal aorta. In this experiment, left ventricular end diastolic diameter(LVIDd), left ventricular end systolic diameter(LVIDs), left ventricular ejection fraction(LVEF), fractional shortening(FS), electrocardiogram and Expression of BNP in serum were used as indexes of chronic heart failure after 8 weeks of operation. After successful modeling, 122 SD rats were randomly divided into sham operation group, model group, high dose group of Fuzi Decoction extracted by water, low, medium and high groups of Fuzi Decoction extracted by 70% ethanol and Captopril group. After 4 weeks of administration, the serum was detected by ELISA. Fuzi Decoction extracted by 70% ethanol could significantly reduce the contents of BNP, NT-proBNP, IL-6, TNF-α, Ang-II, ALD, CK, ET-1, LDH, PRA and CRP in chronic heart failure rats. In the process of cardiac function improvement in chronic heart failure rats, the alcohol extracts in the middle and high dose groups were more effective than tthose of the large doses of water extract. Fuzi Decoction can down-regulate the content of nerve cell factor in chronic heart failure rats by inhibiting activity the renin aldosterone system of angiogenin(RAAS) and regulate nerve endocrine, improve ventricular remodeling and heart function, reduce the symptoms of heart failure.
引文
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[11] 陈荣昌,孙桂波,张强,等. 附子及其复方中药的药理作用研究进展[J]. 中草药,2014,45(6):883-888.
[12] 张秀云,张书珍. 附子汤加味治疗充血性心力衰竭60例[J]. 实用中医内科杂志,2003,17(2):98-99.
[13] 孙秀琴. 加味附子汤治疗阳虚型慢性心功能不全86例[J]. 光明中医,2009,24(7):1294-1295.
[14] 侯晓亮,洪健康,肖雪云,等. 附子汤对慢性心力衰竭患者心功能及血浆NT-pro-BNP的影响[J]. 新中医,2013,45(12):32-34.
[15] 汪谦. 现代医学实验方法[M]. 北京:人民卫生出版社,1998:914.
[16] 贲长恩. 医学科研思路方法与程序[M]. 北京:人民卫生出版社,2009:156.
[17] Cocco G, Jerle P. Assessing the benefits of natriuretic peptides-guided therapy in chronic heart failure[J]. Cardiol J, 2015,22(1):5-11.
[18] 韩额尔德木图,马月宏,王海燕,等. 慢性心衰的病理生理及发病机制研究进展[J].中西医结合心脑血管病杂志,2016,14(12):1349-1352.
[19] Rossi F,Mascolo A,Mollace V. The pathophysiological role of natriuretic peptide-RAAS cross talk in heart failure[J]. International Journal of Cardiology, 2016, 3: 1-5.
[20] 蔡虎志. 温阳振衰颗粒对慢性心衰患者及其对慢性心衰模型兔心肌细胞外信号调节激酶1/2的影响[D]. 长沙:湖南中医药大学,2014.
[21] Kadokami T, Frye C, Lemster B, et al. Anti-tumor necrosis factor-α antibody limits heart failure in a transgenic model[J]. Circulation, 2001, 104(10): 1094-1097.
[22] 罗芳,周宪,梁惠汝.神经内分泌细胞因子在心力衰竭中的作用机制及临床意义[J]. 中国分子心脏病学杂志,2007,7(2):108-111.
[23] Xiong GL, Prybol K, Boyle SH, et al. Inflammation markers and Major Depressive Disorder in Patients with Chronic Heart Failure: Results from the Sertraline Against Depression and Heart Disease in Chronic Heart Failure (SADHART-CHF) study[J]. Psychosom Med,2015,77(7): 808-815.
[24] 刘彬,邹桂,陈齐军,等. 重组人脑利钠肽对急性心肌梗死合并急性心力衰竭患者PCI后心室重构的作用机制探讨[J].临床医学,2014,9(27):71-73.
[25] 丁邦晗,吴晓新,刘云涛,等. “金三角”之下慢性心力衰竭治疗的中西医结合策略[J]. 中国中医基础医学杂志,2015,21(4):436- 456.
[26] 叶周恒,许骥. 醛固酮诱导心室重构作用及机制[J]. 心肺血管病杂志,2011,30(2):174-176.
[2] The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure[J]. N Engl J Med, 1997, 336(8):525-533.
[3] Yancy CW, Jessup M, Bozkurt B, et al. American College of Cardiology Foundation. 2017 ACC/AHA/HFSA Focused 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] Tang WH, Huang Y. Cardiotonic modulation in heart failure: insights from traditional Chinese medicine[J]. J Am Coll Cardiol, 2013, 62(12): 1073-1074.
[5] 张洁,仇盛蕾. 慢性心力衰竭患者中医证候要素相关性研究[J]. 中医学报,2017,32(8):1555-1558.
[6] 李赛美,李宇航. 全国高等医药教材建设研究会规划教材:伤寒论讲义[M]. 北京:中国中医药出版社,2012:287.
[7] 邓中甲. 方剂学[M]. 北京:中国中医药出版社,2011:138.
[8] 韩涛,滕佳琳,王树荣,等. 附子汤对小鼠6-酮-前列腺 F1a、血栓素 B2的影响[J]. 中成药研究,1993(4):31-32.
[9] 黄惠刚,朱奔奔,黄波. 附子汤对慢性充血性心力衰竭模型大鼠BNP,IL-6水平的影响[J]. 陕西中医,2009,30(6):745-746.
[10] 李庆. 附子汤对慢性心力衰竭大鼠心室重构及肾素血管紧张素醛固酮系统的影响[J]. 新中医,2015,47(1):222-224.
[11] 陈荣昌,孙桂波,张强,等. 附子及其复方中药的药理作用研究进展[J]. 中草药,2014,45(6):883-888.
[12] 张秀云,张书珍. 附子汤加味治疗充血性心力衰竭60例[J]. 实用中医内科杂志,2003,17(2):98-99.
[13] 孙秀琴. 加味附子汤治疗阳虚型慢性心功能不全86例[J]. 光明中医,2009,24(7):1294-1295.
[14] 侯晓亮,洪健康,肖雪云,等. 附子汤对慢性心力衰竭患者心功能及血浆NT-pro-BNP的影响[J]. 新中医,2013,45(12):32-34.
[15] 汪谦. 现代医学实验方法[M]. 北京:人民卫生出版社,1998:914.
[16] 贲长恩. 医学科研思路方法与程序[M]. 北京:人民卫生出版社,2009:156.
[17] Cocco G, Jerle P. Assessing the benefits of natriuretic peptides-guided therapy in chronic heart failure[J]. Cardiol J, 2015,22(1):5-11.
[18] 韩额尔德木图,马月宏,王海燕,等. 慢性心衰的病理生理及发病机制研究进展[J].中西医结合心脑血管病杂志,2016,14(12):1349-1352.
[19] Rossi F,Mascolo A,Mollace V. The pathophysiological role of natriuretic peptide-RAAS cross talk in heart failure[J]. International Journal of Cardiology, 2016, 3: 1-5.
[20] 蔡虎志. 温阳振衰颗粒对慢性心衰患者及其对慢性心衰模型兔心肌细胞外信号调节激酶1/2的影响[D]. 长沙:湖南中医药大学,2014.
[21] Kadokami T, Frye C, Lemster B, et al. Anti-tumor necrosis factor-α antibody limits heart failure in a transgenic model[J]. Circulation, 2001, 104(10): 1094-1097.
[22] 罗芳,周宪,梁惠汝.神经内分泌细胞因子在心力衰竭中的作用机制及临床意义[J]. 中国分子心脏病学杂志,2007,7(2):108-111.
[23] Xiong GL, Prybol K, Boyle SH, et al. Inflammation markers and Major Depressive Disorder in Patients with Chronic Heart Failure: Results from the Sertraline Against Depression and Heart Disease in Chronic Heart Failure (SADHART-CHF) study[J]. Psychosom Med,2015,77(7): 808-815.
[24] 刘彬,邹桂,陈齐军,等. 重组人脑利钠肽对急性心肌梗死合并急性心力衰竭患者PCI后心室重构的作用机制探讨[J].临床医学,2014,9(27):71-73.
[25] 丁邦晗,吴晓新,刘云涛,等. “金三角”之下慢性心力衰竭治疗的中西医结合策略[J]. 中国中医基础医学杂志,2015,21(4):436- 456.
[26] 叶周恒,许骥. 醛固酮诱导心室重构作用及机制[J]. 心肺血管病杂志,2011,30(2):174-176.