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

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200～250 g,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340 mg/kg,1次/d,连续2 d,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50 μl,每4 h 1次,持续30 d,夜间停止注射,HTEB组注射0.15%罗哌卡因50 μl,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30 d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-MHC mRNA、β-MHC mRNA的表达水平,并计算α-MHC mRNA和β-MHC mRNA占总MHC mRNA的百分比.结果 与C组比较,其余3组LVEDD增大,LVEF降低,α-MHC mRNA表达下调,β-MHC mRNA表达上调,α-MHC mRNA占MHC mRNA百分比降低,β-MHC mRNA占总MHC mRNA的百分比升高(P<0.05);与HF组比较,HTEB组α-MHC mRNA表达上调,β-MHC mRNA表达下调,α-MHC mRNA占MHC mRNA百分比升高,β-MHC mRNA占MHC mRNA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.

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

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 die epidural space from T3 or T4 level to T1 level in group NS and HTEB. In group NS and HTEB, 0.9% normal saline 50 μl and 0.15% ropivacaine 50 μl were injected through the microspinal catheter every 4 h in the daytime for 30 d respectively. Left ventricular eml-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.