PPAR-α的激活对心力衰竭早期心肌功能的机制研究  

Mechanism of activation of PPAR-α in myocardial function in the early stage of heart failure

作　　者：王理亚 单艳华 刘永萍 孙丁 WANG Liya;SHAN Yanhua;LIU Yongping;SUN Ding(General Intensive Care Medicine Department,Zhumadian City Central Hospital,Zhumadian,Henan 463000,China;The Cardiovascular and Critical Care Medicine De-partment,Zhumadian City Central Hospital,Zhumadian,Henan 463000,China)

机构地区：[1]驻马店市中心医院综合重症医学科,河南驻马店463000 [2]驻马店市中心医院心血管重症医学科,河南驻马店463000

出　　处：《安徽医药》2022年第4期754-759,I0002,共7页Anhui Medical and Pharmaceutical Journal

摘　　要：目的 研究过氧化物酶体增殖物激活受体-α(PPAR-α)的激活在心力衰竭早期中的作用,并揭示其作用机制。方法2018年1月至2020年1月,通过横向主动脉缩窄(TAC)手术构建心力衰竭模型,将20只C57BL/6小鼠按随机数字表法随机分为TAC-DTG组、TAC-tTA组、Sham-DTG组、Sham-tTA组,每组5只。TCA术后5周用高效液相色谱法(HPLC)检测ATP并计算磷酸肌酸/ATP水平;TAC术后8周用逆转录-聚合酶链反应(RT-PCR)法检测PPAR-α及其靶基因的mRNA表达;用经胸超声心动图检测左心室舒张末期内径(LVDd)、舒张期LV后壁(LVPWd)及射血分数(EF);检测心脏重量与体重和胫骨长度及肺部重量与胫骨长度的比值(HW/BW、HW/TL、LW/TL);用Masson Trichrome染色检测心肌细胞横截面积、心肌纤维化程度;RT-PCR法检测脑钠肽(BNP)、I型胶原α1(Colla1)、Ⅲ型胶原α1(Col3a1)mRNA表达;用离体心脏灌流实验检测棕榈酸氧化速率、葡萄糖氧化速率。结果 TAC术后5周,TAC-DTG组小鼠ATP浓度[(13.33±0.83)nmol/mg比(9.56±1.05)nmol/mg]和磷酸肌酸/ATP水平[(2.21±0.13)比(1.66±0.09)]均明显高于TAC-tTA组;TAC术后8周,TAC组小鼠PPAR-α[(0.64±0.05)比(1.00±0.04)]、CPT1[(0.56±0.06)比(1.00±0.06)]、FATP1[(0.40±0.05)比(1.00±0.07)]、CD36[(0.76±0.15)比(1.00±0.20)]mRNA表达水平均明显高于Sham组小鼠;TAC组小鼠LVDd[(4.41±0.07)mm比(4.02±0.10)mm]、LVPWd[(0.87±0.02)mm比(0.74±0.01)mm]、EF[(37.22±1.90)%比(64.91±2.34)%]较Sham组小鼠明显减弱;TAC-DTG组小鼠HB/BW[(6.26±0.18)比(7.21±0.29)]、HW/TL[(8.80±0.27)比(10.56±0.54)]、LW/TL[(13.67±0.76)比(16.97±1.25)]较TAC-tTA组小鼠明显减弱;TAC-DTG组小鼠心肌细胞横截面积[(694.64±23.31)μm3比(766.90±20.98)μm3]、心肌纤维化程度[(4.25±0.99)%比(8.24±1.08)%]较TAC-tTA组小鼠明显减小;TAC-DTG组小鼠BNP[(5.29±1.02)比(9.33±1.42)]、Col1a1[(2.76±0.19)比(4.40±0.33)]、Col3a1[(3.08±0.21)比(7.80±2.05)]mRNA表达水平较TAC-tTA组小鼠明显降低;TAC-DTG�Objective To study the role of activation of peroxisome proliferator-activated receptor-α(PPAR-α) in the early stage of heart failure and to reveal its mechanism of action.Methods From January 2018 to January 2020,A heart failure model was established by transverse aortic coarctation (TAC) surgery,and 20 C57BL/6 mice were randomly assigned into TAC-DTG group,TAC-tTA group,Sham-DTG group,and Sham-tTA group according to the random number table method,5 cases in each group.High performance liquid chromatography (HPLC) was used to detect ATP and creatine phosphocreatine/ATP levels at 5 weeks after TCA.PPAR-αand its mRNA expression of target genes were detected by reverse transcription-polymerase chain reaction (RT-PCR) at 8 weeks after TAC.Left ventricular end-diastolic diameter (LVDd),LV posterior wall in diastole (LVPWd) and ejection fraction (EF) were measured by transthoracic echocardiography.The ratio of heart weight with body weight and tibia length,and the ratio of lung weight with tibia length (HW/BW,HW/TL,LW/TL) were measured.The cross-sectional area of cardiomyocytes and the degree of myocardial fibrosis were detected by Masson Trichrome staining.The mRNA expression of brain natriuretic peptide (BNP),type I collagenα1 (Colla1) and typeⅢcollagenα1 (Col3a1) were detected by RT-PCR.The rate of palmitic acid oxidation and glucose oxidation were detected by isolated heart perfusion experiment.Results 5 weeks after TAC,the ATP concentration[(13.33±0.83) nmol/mg vs.(9.56±1.05) nmol/mg]and phosphocreatine/ATP levels[(2.21±0.13) vs.(1.66±0.09)]were significantly higher than those in the TAC-tTA group.8 weeks after TAC,the PPAR-α[(0.64±0.05) vs.(1.00±0.04)],CPT1[(0.56±0.06) vs.(1.00±0.06)],FATP1[(0.40±0.05) vs.(1.00±0.07)],CD36[(0.76±0.15) vs.(1.00±0.20)]mRNA expression levels were significantly higher than those in the Sham group.The LVDDd[(4.41±0.07)mm vs.(4.02±0.10) mm],LVPWd[(0.87±0.02) mm vs.(0.74±0.01) mm],EF[(37.22±1.90)%vs.(64.91±2.34)%]of mice in the TAC group were significantly wea

关 键 词：心力衰竭 过氧化物酶体增殖物激活受体 脂肪酸氧化 离体心脏灌流 心肌功能 

分 类 号：R541.6[医药卫生—心血管疾病]