目的? 探讨短链酰基辅酶A脱氢酶(SCAD)在大鼠心肌梗死(心梗)后心力衰竭(心衰)中的变化,以及有氧运动对其的干预作用.方法? 按随机数字表法将健康雄性SD大鼠分为假手术组(Sham组)、假手术游泳组(Sham+swim组)、心衰模型组(LAD组)、心衰游泳组(LAD+swim组),每组9只.采用冠状动脉左前降支结扎法(LAD)制备心梗后心衰大鼠模型;Sham组只在左冠状动脉下穿线打一个松结,其余操作同LAD组.Sham+swim组和LAD+swim组大鼠于术后预游泳1周(从第1天训练15?min逐渐增加到第5天的60?min),再进行游泳耐力训练(从第2周开始每日持续训练60?min,每周6次,连续10周).于游泳耐力训练前测定大鼠尾动脉收缩压(SBP),以后每隔2周测定1次,直至第10周结束.游泳训练10周后,用超声心动图测量心排血量(CO)、每搏量(SV)、左室射血分数(LVEF)、缩短分数(FS)、左室收缩期末内径(LVESD)、左室舒张期末内径(LVEDD)、左室收缩期末容积(LVESV)、左室舒张期末容积(LVEDV);用Masson染色法观察心脏形态学改变;用原位末端缺刻标记法(TUNEL)检测心肌细胞凋亡情况并计算凋亡指数(AI);用反转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹试验(Western?Blot)分别检测心肌SCAD的mRNA及蛋白表达;另外,按试剂盒步骤检测心肌SCAD活性、三磷酸腺苷(ATP)含量以及血清和心肌游离脂肪酸(FFA)含量.结果? 与Sham组比较,Sham+swim组SBP无明显变化,心肌出现生理性肥大(离心性肥大),心肌收缩力增强;LAD组呈持续性低血压状态,心梗明显,左室变薄,心肌舒缩功能减退.与LAD组相比,LAD+swim组血压、心脏舒缩功能及心梗得到明显改善〔SBP(mmHg,1?mmHg=0.133?kPa):4周为119.5±4.4比113.2±4.5,6周为120.3±4.0比106.5±3.7,8周为117.4±1.3比111.0±2.3,10周为126.1±1.6比119.4±1.9 ;CO(mL/min):59.10±6.31比33.19±4.76,SV(μL):139.42±17.32比84.02±14.26,LVEF:0.523±0.039比0.309±0.011,FS:(28.17±2.57)%比(15.93±3.64)%,LVEDD?(mm):8.80±0.19比9.35±0.30,LVESD(mm):5.90±0.77比7.97±0.60,LVEDV(μL):?426.57±20.84 比 476.24±25.18,LVESV(μL):209.50±25.18 比 318.60±16.10 ;AI :(20.4±1.4)% 比(31.2±?4.6)%;均P<0.05〕.与Sham组相比,Sham+swim组心肌SCAD的mRNA和蛋白表达、SCAD活性明显升高,ATP?含量略有升高,血清FFA含量明显下降,心肌FFA含量略有减少;LAD组心肌SCAD的mRNA和蛋白表达、SCAD?活性、ATP含量均明显降低,血清和心肌FFA含量明显增高.与LAD组相比,LAD+swim组心肌SCAD的mRNA?和蛋白表达、ATP含量明显升高〔SCAD?mRNA(2-ΔΔCt):0.52±0.16比0.15±0.01,SCAD/GAPDH(以Sham组为?参照,倍数):0.94±0.08比0.60±0.11,ATP含量(μ mol/g):52.8±10.1比14.7±6.1,均P<0.05〕,血清和心肌FFA?含量明显减少〔血清FFA(nmol/L):0.11±0.03比0.29±0.04,心肌FFA(nmol/g):32.7±8.2比59.7±10.7,均P<?0.05〕,SCAD活性略有升高(kU/g:12.3±4.3比8.9±5.8,P>0.05).结论? SCAD在大鼠心梗后心衰中的表达明显?下调,有氧运动干预后其表达明显上调,表明有氧运动可能通过上调?SCAD表达改善心梗后心衰的严重程度.
Objective? To?Study?the?changes?of?short-chain?acyl-CoA?dehydrogenase?(SCAD)?in?heart?failure?(HF)?after?myocardial?infarction?(MI),?and?the?effect?of?aerobic?exercise?on?SCAD.? Methods? Healthy?male?Sprague-Dawley?(SD)?rats?were?divided?into?sham?operation?group?(Sham?group),?sham?operation?swimming?group?(Sham+swim?group),?HF?model?group?(LAD?group)?and?HF?swimming?group?(LAD+swim?group)?by?random?number?table?method,?with?9?rats?in?each?group.?The?left?anterior?descending?branch?of?coronary?artery?(LAD)?was?ligated?to?establish?a?rat?model?of?HF?after?MI.?In?Sham?group,?only?one?loose?knot?was?threaded?under?the?left?coronary?artery,?and?the?rest?operations?were?the?same?as?those?in?LAD?group.?Rats?in?Sham+swim?group?and?LAD+swim?group?were?given?swimming?test?for?1?week?after?operation?(from?15?minutes?on?the?1st?day?to?60?minutes?on?the?5th?day).?Then?they?were?given?swimming?endurance?training?(from?the?2nd?week?onwards,?60?minutes?daily,?6?times?weekly,?10?weeks?in?a?row).?Tail?artery?systolic?pressure??(SBP)?was?measured?before?swimming?endurance?training?and?every?2?weeks?until?the?end?of?the?10th?week.?Ten?weeks?after?swimming?training,?echocardiography?was?performed?to?measure?cardiac?output?(CO),?stroke?volume?(SV),?left?ventricular?ejection?fraction?(LVEF),?shortening?fraction?(FS),?left?ventricular?end-systolic?diameter?(LVESD),?left?ventricular?end-diastolic?diameter?(LVEDD),?left?ventricular?end-systolic?volume?(LVESV),?and?left?ventricular?end-diastolic??volume?(LVEDV).?Morphological?changes?of?heart?were?observed?by?Masson?staining.?Apoptosis?of?myocardial?cells?was?detected?by?transferase-mediated?deoxyuridine?triphosphate-biotin?nick?end?labeling?stain?(TUNEL)?and?apoptosis?index?(AI)?was?calculated.?Reverse?transcription-polymerase?chain?reaction?(RT-PCR)?and?Western?Blot?were?used?to?detect?the?mRNA?and?protein?expression?of?myocardial?SCAD?respectively.?In?addition,?the?enzyme?activity?of?SCAD,?the?content?of?adenosine?triphosphate?(ATP)?and?free?fatty?acid?(FFA)?in?serum?and?myocardium?were?detected?according?to?the?kit?instruction?steps.? Results? Compared?with?Sham?group,?Sham+swim?group?showed?SBP?did?not?change?significantly,?with?obvious?eccentric?hypertrophy?and?increased?myocardial?contractility,?and?LAD?group?showed?persistent?hypotension,?obvious?MI,?thinning?of?left?ventricle,?and?decreased?myocardial?systolic/diastolic?function.?Compared?with?LAD?group,?SBP,?systolic/diastolic?function?and?MI?in?LAD+swim?group?were?significantly?improved?[SBP?(mmHg,?1?mmHg?=?0.133?kPa):?119.5±4.4?vs.?113.2±4.5?at?4?weeks,?120.3±4.0?vs.?106.5±3.7?at??6?weeks,?117.4±1.3?vs.?111.0±2.3?at?8?weeks,?126.1±1.6?vs.?119.4±1.9?at?10?weeks;?CO?(mL/min):?59.10±6.31?vs.?33.19±4.76,?SV?(μL):?139.42±17.32?vs.?84.02±14.26,?LVEF:?0.523±0.039?vs.?0.309±0.011,?FS:?(28.17±2.57)%?vs.?(15.93±3.64)%,?LVEDD?(mm):?8.80±0.19?vs.?9.35±0.30,?LVESD?(mm):?5.90±0.77?vs.?7.97±0.60,?LVEDV?(μL):?426.57±20.84?vs.?476.24±25.18,?LVESV?(μL):?209.50±25.18?vs.?318.60±16.10;?AI:?(20.4±1.4)%?vs.?(31.2±4.6)%;?all?P?0.05].?Compared?with?Sham?group,?the?mRNA?and?protein?expression?of?myocardium?SCAD,?the?activity?of?SCAD?in?Sham+swim?group?were?significantly?increased,?the?content?of?ATP?was?slightly?increased,?the?content?of?serum?FFA?was?significantly?decreased,?and?the?content?of?myocardial?FFA?was?slightly?decreased;?conversely,?the?mRNA?and?protein?expression?of?myocardium?SCAD,?the?activity?of?SCAD?and?the?content?of?ATP?in?LAD?group?were?significantly?decreased,?the?content?of?serum?and?myocardial?FFA?were?significantly?increased.?Compared?with?LAD?group,?the?mRNA?and?protein?expression?of?myocardium?SCAD,?the?content?of?ATP?were?significantly?increased?in?LAD+swim?group?[SCAD?mRNA?(2-ΔΔCt):?0.52±0.16?vs.?0.15±0.01,?SCAD/GAPDH?(fold?increase?from?Sham?group):?0.94±0.08?vs.?0.60±0.11,?ATP?content?(μmol/g):?52.8±10.1?vs.?14.7±6.1,?all?P?0.05],?the?content?of?serum?and?myocardial?FFA?were?significantly?decreased?[serum?FFA?(nmol/L):?0.11±0.03?vs.?0.29±0.04,?myocardial?FFA?(nmol/g):?32.7±8.2?vs.?59.7±10.7,?both?P?0.05],?and?the?activity?of?SCAD?was?slightly?increased?(kU/g:?12.3±4.3?vs.?8.9±5.8,?P?>?0.05).? Conclusion? The?expression?of?SCAD?in?HF?was?significantly?down-regulated,?and?the?expression?was?significantly?up-regulated?after?aerobic?exercise?intervention,?indicating?that?swimming?may?improve?the?severity?of?HF?by?up-regulating?the?expression?of?SCAD.