上胸段硬膜外阻滞对心肌梗死后心力衰竭大鼠心室重构及β3肾上腺素能受体的影响

Effects of high thoracic epidural anesthesia on ventricular remodeling and expression of β3- adrenoceptor in rats with heart failure induced by acute myocardial infarction

目的观察上胸段硬膜外阻滞对大鼠心肌梗死后心室重构和心功能的影响，并探讨其机制。方法模型成功的大鼠随机分为假手术组（S组，n=12）、心力衰竭组（CHF组，n=24）和硬膜外阻滞组（HTEA组，n=24）。硬膜外置管术后24hS组和CHF组于硬膜外腔注入9g／L生理盐水（100μL／kg，2次／d，连续4周）。HTEA组于硬膜外腔注入1．25g／L布比卡因（100μl／kg，2次／d，连续4周）。4周后行超声心动图测定左室舒张末期内径（LYEDD）、左室收缩末期内径（LVESD）左室射血分数（LVEF）和左室短轴缩短率（LVES）；测量心脏和左心室质量，计算心脏指数（HW／BW）和左心室指数（LVW／BW）；左室心肌组织HE和Masson染色；RT—PCR测定左室心肌风AR和eNOSmRNA；免疫组织化学检测左室心肌β3AR表达。结果LVEDD和LVESD：HTEA组较CHF组明显缩小（P〈0．01）；LVEF和LVFS：HTEA组较CHF组明显增加（P〈0．05）。HW／BW和LVW／BW：CHF组和HTEA组均明显大于S组（P〈0．01），但HTEA组较CHF组明显减小（P〈0．01）。心肌病理学形态学显示：CHF组心肌细胞变性、萎缩，心肌纤维紊乱、断裂，胶原纤维明显增多，HTEA组心肌细胞变性明显减少，非梗死区心肌纤维化明显改善；与CHF组相比，HTEA组艮AR和eNOSmRNA表达明显减少（P〈0．01）。结论HTEA治疗可以改善或减缓急性心肌梗死后大鼠的左室重构和心功能，可能与其下调β3AR表达有关。

Objective To investigate the effect of high thoracic epidural anesthesia on ventricular remodeling and cardiac function in rats with heart failure induced by myocardial infarction, and to investigate their mechanism. Methods Rats that had been established successively model were randomly divided into S group （n = 12）, HTEA group and CHF group （2d/group）. 9.0 g/L normal sodium 100 μl/kg was injected to epidural cavity twice a day separately in group S and group CHF. 1.25 g/L bupivacaine 100 μL/kg was injected to epidural cavity twice a day in group HTEA. Epidural injection was started 24 hrs after the epidural surgery and continued 4 weeks. Then the change of cardiac function was observed by using echocardiogram. The ratio of heart weight to body weight （HW/BW） and the ratio of left ventricular weight to body weight （LVW/BW） were measured. Noninfarct ventricular tissue were stained with hematoxylin-eosin （HE） and Masson＇s trichrome respectively. β3-adrenoceptor levels and eNOS levels were detected with reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemistry. Results LVEDD and LVESD were significantly decreased in the group HTEA compared with group CHF （P 〈 0. 01 ）, while INEF% and LVFS% were significantly increased （ P 〈 0. 01 ）. The ratios HW/BW and LVW/BW were significantly increase in the group CHF compared with the group S （ P 〈0. 01 ）, but they were limited in the group HTEA （P 〈0. 01 ）. Hypertrophy and edema, degeneration and necrosis of myocytes can be seen in rats with CHF, as well as muscle fibers disruption and collagen fiber increase, while the pathological morphous were attenuated in HTEA rats. β3AR and eNOS mRNA levels were significantly decreased in the group THEA compared with the group CHF. Conclusions These results indicate that HTEA could ameliorate ventricular remodeling and cardiac function in rats with heart failure induced by myocardial infarction. The mechanism could involve decreases of β3 AR expression in rats of heart failure.