运动性心肌顿抑的发生及其能量代谢障碍机制研究
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摘要
研究目的
     研究运动致心肌顿抑及运动性心肌顿抑(EIMS)能量代谢障碍可能机制。
     研究方法
     实验一:24只SD大鼠分为安静对照组(A,n-8)和运动组(B,n=14),B组完成大负荷运动后即刻视心电图情况又分为心电异常组(B1,n=8)和心电正常组(B2,n=6),测定运动前、运动后0、5、10、15、20、30、50、70、90、110min心电图和左室收缩功能;再于运动后110min行HE染色。实验二:24只SD大鼠分为安静对照组(A,n=8),EIMS+去离子水组(C,n=8)和EIMS+ATP组(D,n=8),测定心肌线粒体呼吸功能、心肌AMP、ATP含量、AMPK活性、M-CPT-I mRNA、MCAD mRNA、MEF2a mRNA、GLUT4 mRNA和PGC-1a、PPARa、GLUT4蛋白。
     研究结果:
     (1)大负荷运动诱发大鼠心电可逆性异常,表现为J点值、T波值等改变。
     (2)大负荷运动后B1组LVESP、+dp/dtmax出现两次升降现象,第二次升降为心肌顿抑现象发生,B2组未见明显第二次升降变化。
     (3)三组HE染色评分组间无显著性差异。
     (4)与A组比较,C组心肌ATP显著下降,AMP、AMP/ATP、AMPK活性、α-MHC mRNA、α-MHCmRNA/β-MHCmRNA、LVESP均显著增加, M-CPT-I mRNA、MCAD mRNA、MEF2a mRNA、GLUT4 mRNA、GLUT4蛋白均显著升高,FFA减少;线粒体PGC-1a、PPARa蛋白增加;与C组比较,D组补充ATP后心肌ATP显著升高,AMP无显著性差异,AMP/ATP、AMPK活性、MEF2a mRNA、GLUT4 mRNA、GLUT4蛋白均显著下降,α-MHC mRNA、α-MHCmRNA/β-MHCmRNA、LVESP、M-CPT-I mRNA、MCAD mRNA显著升高;β-MHC mRNA无显著性差异,FFA显著减少;PGC-1a、PPARa均有显著差异
     研究结论:
     (1)大负荷运动可诱发运动性心肌顿抑发生,表现为心电异常、短时可逆性心肌功能障碍、心肌组织无明显坏死,这些变化与临床缺氧缺血所致心肌顿抑相似。
     (2)心肌细胞能量代谢障碍是运动性心肌顿抑发生的可能机制之一,通过补充ATP可以减轻运动性心肌顿抑程度。
Objective
     Research myocardial stunning induced by high intensity exercise and its energy metabolism disorders mechanism of EIMS.
     Methods
     ExpⅠ:24 SD rats were divided into control group (A,n=8) and exercise group (B,n=14).According to the exercise reseal electrocardiogram,group B were divided into ECG abnormalities group (B1,n=8) and ECG normal group (B2,n=6),we determinated electrocardiogram and cardiac function at before exercise,after exercise 0,5,10,15,20,30,50,70,90 and 110min respectively,And analysis HE in 110min after exercise.ExpⅡ:24 SD rats were divided into control group(A,n=8),EIMS+H2O2(C,n=8)and EIMS+ATP(D,n=8),we determinated myocardial mitochondria ST3、ST4 and RCR, myocardial AMP content,ATP content,AMPK activity,M-CPT-I mRNA,MEF2a mRNA,MCAD mRNA,GLUT4 mRNA and PGC-1a,PPARa,GLUT4 protein.
     Results
     (1) High intensity exercise induced ECG reversibly abnormalities,performance for J spot value,T wave value changes.
     (2) LVESP and+dp/dtmax of group B1 appear twice lifting phenomenon after high intensity exercise,the second lifting change for myocardial stunning,group B2 has not seen the obviously second lifting changes.
     (3) Comparison between groups,HE dyeing non-significance difference.
     (4) Compared with group A,myocardial ATP content of group C dropped significantly,AMP content of group C,AMP/ATP of group C,AMPK-activity of group C,α-MHCmRNA of group C,α-MHCmRNA/β-MHCmRNA of group C,LVESP of group C all were significantly increased,M-CPT-ImRNA,MEF2a mRNA, GLUT4 mRNA MCAD mRNA,GLUT4 protein of group C all were significantly increased,FFA content of group C was lossed.Myocardial mitochondria PGC-1a,PPARa protein expression were increased.Compared with group C, group D(ATP supplement),myocardial ATP content of group D was very significant rise,AMP content non-significance difference, AMP/ATP,AMPK activity, MEF2a mRNA,GLUT4 mRNA,GLUT4 protein are significantly,a-MHC mRNA,a-MHC mRNA/β-MHC mRNA,LVESP,M-CPT-I mRNA,MCAD mRNA all were significantly increased;(3-MHC mRNA non-significance difference,FFA content was significantly reduced;Mitochondria PGC-1a,PPARa were significant.
     Conclusion
     (1) High intensity exercise can induce mayocardium stunned,performance characteristics:ECG abnormal,short-term reversible myocardial dysfunction and myocardial tissue dyeing does not change significantly,these characteristics were similared with clinical myocardial stunning performance characteristics.
     (2) Myocardial cell energy metabolization disorders is one of EIMS possible mechinisms,we can promote EIMS myocardial recovery via ATP supplement.
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