高位胸段硬膜外阻滞对心力衰竭大鼠心肌肌球蛋白重链表达的影响

Effects of high thoracic epidural blockade on myocardial myosin heavy chain expression in rats with heart failure

目的探讨高位胸段硬膜外阻滞（HTEB）对心力衰竭大鼠心肌肌球蛋白重链（MHC）表达的影响。方法健康雄性Wistar大鼠28只，体重200—250g，随机分为4组，每组7只：对照组（C组）、心力衰竭组（HF组）、HTEB组和生理盐水组（NS组）。皮下注射异丙肾上腺素340mg/kg，1次／d，连续2d，制备心力衰竭模型，注射后第8周NS组和HTEB组经T3或T4水平硬膜外置入微导管至T1水平，NS组经微导管注射0．9％生理盐水50μl，每4h1次，持续30d，夜间停止注射，HTEB组注射0．15％罗哌卡因50μl，方法同前。于皮下注射异丙肾上腺后第8周且硬膜外注药前（T1）和硬膜外注药30d后（T2）测定大鼠左心室舒张末期内径（LVEDD）和左室射血分数（LVEF），于T2时观察心肌组织和肺组织病理学结果，测定α—MHCmRNA、β-MHCmRNA的表达水平，并计算α-MHCmRNA和β—MHCmRNA占总MHCmRNA的百分比。结果与C组比较，其余3组LVEDD增大，LVEF降低，α—MHCmRNA表达下调，β—MHCmRNA表达上调，α-MHCmRNA占MHCmRNA百分比降低，β—MHCmRNA占总MHC mRNA的百分比升高（P〈0．05）；与HF组比较，HTEB组α＋MHCmRNA表达上调，β—MHCmRNA表达下调，α-MHCmRNA占MHCmRNA百分比升高，β—MHCmRNA占MHCmRNA百分比降低（P〈0．05），NS组上述指标差异无统计意义（P〉0．05）；与T1时比较，HTEB组LVEF升高（P〈0．05），LVEDD差异无统计学意义（P〉0．05），HTEB组心肌和肺组织病理学改变较轻。结论HTEB改善心力衰竭大鼠心肌收缩功能的机制可能与纠正α—MHC和β-MHC表达比例的异常有关。

Objective To investigate the effects of high thoracic epidural blockade （HTEB） on myocardial myosin heavy chain （MHC） expression in the rats with heart failure. Methods Twenty-eight male Wistar rats, weighing 200-250 g, were randomly divided into 4 groups （ n = 7 each） ： control group （group C）, heart failure group （group HF）, HTEB group and normal saline group （group NS）. Heart failure was induced by subcutaneous injection of isoprenaline 340 mg/kg once a day for 2 days. After 8 weeks, a microspinal catheter was inserted into the epidural space from T3 or T4 level to T1 level in group NS and HTEB. In group NS and HTEB, 0.9% normal saline 50μl and 0.15% ropivacaine 50 μl were injected through the microspinal catheter every 4 h in the daytime for 30 d respectively. Left ventficular end-diastolic diameter （LVEDD） and left ventricular ejection fraction （LVEF） were measured 8 weeks after injection of isoprenaline （T1） and 30 d after epidural administration （T2）. Pathological results of myocardial and lung tissues were observed, the expression of α-MHC mRNA and β-MHC mRNA was measured by RT-PCR and the percentage of mRNA coding for α-MHC and β-MHC in total MHC mRNA was calculated at T2 . Results Compared with group C, LVEDD was increased, LVEF decreased, α-MHC mRNA expression down-regulated while β-MHC mRNA expression up-regulated, and the ratio of α-MHC mRNA to MHC mRNA decreased while the ratio of β-MHC mRNA to MHC mRNA increased in the other 3 groups （P 〈 0.05） . α-MHC mRNA expression was significantly higher, β-MHC mRNA expression lower, the ratio of α-MHC mRNA to MHC mRNA higher, and the ratio of β-MHC mRNA to MHC mRNA lower in group HTEB than in group HF （ P 〈 0.05）, but there was no significant difference in the above parameters between group NS and HF （ P 〉 0.05）. LVEF in group HTEB was significantly higher at T2 than at T1 （ P 〈 0.05） while there was no significant difference in LVEDD between T2 and T1 in group HTEB （ P 〉 0.05）. Pathological changes in myocardial and lung tissues in group HTEB were milder at T2 than at T1 . Conclusion HTEB can improve cardiac function by correcting abnormal expression ratio of α-MHC to β-MHC in rats with heart failure.