叶子青,苏一飞,赵静,李小兵,傅思莹,洪永敦
YE Ziqing,SU Yifei,ZHAO Jing,LI Xiaobing,FU Siying,HONG Yongdun

• 1:广州中医药大学第一附属医院
• 2:广东省高州市中医院

摘要(Abstract)：

目的观察保心康与常规药物疗法联用对慢性心力衰竭模型大鼠的心肌线粒体DNA及COX酶活性的影响。方法选用60只SD大鼠随机分为假手术组、模型组、保心康组、常规治疗组、常规治疗+保心康组、常规治疗+曲美他嗪组。采用腹主动脉缩窄术复制慢性心力衰竭大鼠模型。各治疗组分别给予保心康(1 020 mg/kg)、常规治疗(美托洛尔10 mg/kg、卡托普利5 mg/kg、地高辛0.022 5 mg/kg)、曲美他嗪(10 mg/kg)6周,以心脏彩超测定各组大鼠的心功能后处死取心肌组织,以q PCR测定线粒体DNA缺失率、光谱法测定线粒体COX酶活性。结果保心康组COX酶活性高于模型组(P<0.05),保心康组与常规治疗组间COX酶活性则无显著性差异(P>0.05)。常规治疗+保心康组COX酶活性高于常规治疗组(P<0.01)。常规治疗+曲美他嗪组与模型组比较,mtDNA缺失率较低(P<0.01)。其它各药物治疗组与模型组相比较,mtDNA缺失率无显著性差异(P>0.05)。结论提示保心康可能通过保护心肌COX酶活性来改善衰竭心肌的能量代谢障碍,但其对COX酶活性的改善并不是通过保护编码COX酶的mtDNA来实现的。
OBJECTIVE To observe the effect of Baoxinkang formula combined with standard pharmacologic therapy in preservation of myocardial mitochondrial DNA and the activity of cytochrome C oxidase in chronic heart failure rat model. METHODS A total of 60 SPF level Sprague-Dawley rats( SD rats,half male and half female) were randomly divided into 6 groups: the Baoxinkang group( Group 1),the standard therapy group( Group 2),the Baoxinkang and standard therapy group( Group 3),the trimetazidine and standard therapy group( Group 4),control group( Group 5) and sham-operation group( Group 6). For Group 1 to 5,abdominal aortic banding were perform while for Group 6 only sham-operation. 6 weeks after the operation,Group 1 to 4 started intragastric administration with certain medicine( Group 1: Baoxinkang 1 020 mg / kg; Group 2: Metoprolol 10 mg / kg,Captopril 5 mg / kg,Digoxin0.022 5 mg / kg; Group 3: Baoxinkang 1 020 mg / kg,Metoprolol 10 mg / kg,Captopril 5 mg / kg,Digoxin 0. 022 5 mg / kg; Group 4:Metoprolol 10 mg / kg, Captopril 5 mg / kg, Digoxin 0. 022 5 mg / kg, Trimetazidine 10 mg / kg). After 6 weeks of intragastric administration,echocardiography was performed on all rats before euthanatization. The myocardial mitochondrial DNA was examined with q PCR,while the activity of cytochrome C oxidase was examined by spectrometry. All data was analyzed by SPSS 13.0. RESULTS The activity of cytochrome C oxidase in Group 1 was higher than that in Group 5( P<0.05). There was no significant difference of the activity of cytochrome C oxidase between Group 1 and Group 2( P>0.05). The activity of cytochrome C oxidase in Group 3 was higher than that in Group 2( P<0.01). The mt DNA was less damaged in Group 4 than in Group 5( P < 0.01). No significant difference was observed of the mt DNA damage in between Group 1,Group 2,Group 3 and Group 5( P>0.05).CONCLUSION Baoxinkang formula may improve metabolic disorder in failing heart by preserving the activity of cytochrome C oxidase. But the preservation of the activity of cytochrome c oxidase may not achieved by preserving the mt DNA that code the cytochrome C oxidase.

关键词(KeyWords)： R97慢性心力衰竭;药物治疗;大鼠模型;线粒体DNA;COX酶活性
chronic heart failure;pharmacological therapy;rat model;mitochondrial DNA;cytochrome C oxidase

Abstract:

Keywords:

基金项目(Foundation): 广东省科技计划项目(2011B031700073);; 广东省临床用药研究基金—施慧达基金项目(2013X30)

作者(Author): 叶子青,苏一飞,赵静,李小兵,傅思莹,洪永敦
YE Ziqing,SU Yifei,ZHAO Jing,LI Xiaobing,FU Siying,HONG Yongdun

参考文献(References)：

• [1]Katz AM.Cellular mechanisms in congestive heart failure[J].Am J Cardiol,1988,62(2):3A-8A.
• [2]van Bilsen M,Smeets PJH,Gilde AJ,et al.Metabolic remodeling of the failing heart:the cardiac burn-out syndrome?[J].Cardiovascular Research,2004,61:218-226.
• [3]陈宇鹏,冼绍祥,黄衍寿.保心康对家兔实验性心功能不全动物模型的药效学研究[J].广州中医药大学学报,2002,19(1):36.
• [4]冼绍祥,杨忠奇,汪朝辉,等主编.心力衰竭中西医结合研究基础与临床[M].上海:上海科技出版社,2011:83-96.
• [5]徐叔云,卞如濂,陈修.药理实验方法学[M].北京:人民卫生出版社,2002:202-204.
• [6]洪永敦,苏一飞,叶子青,等.保心康联合常规药物干预对心力衰竭模型大鼠心功能及腺苷酸代谢的影响[J].广州中医药大学学报,2015,32(1):99.
• [7]Garnier A,Fortin D,Delomenie C,et al.Depressed Mitochondrial Transcription Factors and Oxidative Capacity in Rat Failing Cardiac and Skeletal Muscles[J].J Physiol,2003,551(2):491-501.
• [8]钟宁,张翼,朱海峰,等.间隙性低氧防止缺血再灌注损伤引起的线粒体结构损伤和mt DNA片段缺失[J].Acta Physiologica Sinica.2000;53(5):375-380.
• [9]Beeltran B,Mathur A,Duchen MR,et al.The effect of nitric oxide on cell respiration:a key to understanding its role in cell survival or death[J].Proc Natl Acad Sci USA,2000,97:14602-14607.
• [10]Wu C,Yan L,Depre C,et al.Cytochrome c Oxidase III as a mechanism for apoptosis in heart failure following myocardial infarction[J].Am J Physiol Cell Physiol,2009,297(4):C928-C934.
• [11]Mervaala E,Biala A,Merasto S,et al.Metabolomics in Angiotensin II-Induced Cardiac Hypertrophiy[J].Hypertension,2010,55:508-515.
• [12]Ide T,Tsutsui H,Hayashidani S,et al.Mitochondrial DNA Damage and Dysfunction Associated With Oxidative Stress in Failing Hearts After Myocardial Infarction[J].Circ Res,2001,88:529-535.
• [13]Garcia-Marin J,Goldenthal MJ,Pierpont ME,et al.Impaired Mitochondrial Function in idiopathic Dilated Cardiomyopathy:Bio-chemical and molecular analysis[J].Cardiac Failure,1995,1:285-288.
• [14]Sanbe A,Tanonaka K,Kobayasi R,et al.Effects of Longterm Therapy with ACE Inhibitors,Captopril,Enalapril and Trandolapril,on Myocardial Energy Metabolism in Rats with Heart Failure Following Myocardial Infarction[J].JMCC,1995,27:2209-2222.