胰岛素对大鼠心肌梗死后心室重构和心脏功能的影响及其机制

目的:探讨胰岛素对大鼠心肌梗死(MI)后心室重构和心脏功能的影响及其机制。方法: 80只成年雄性Sprague-Dawley大鼠行冠状动脉左前降支(LAD)结扎制备MI模型，随机分为5组:即假手术(Sham)组(n=20)、生理盐水对照(MI+NS)组(n=20)、胰岛素治疗(MI+Ins)组(n=20)、肿瘤坏死因子α(TNF-α)拮抗剂益赛普治疗(MI+En)组(n=10)及Ins+En治疗(MI+Ins+En)组(n=10)。用ELISA法检测各组大鼠在MI后1周和4周时，心肌及血清TNF-α的水平。超声心动图测定各组大鼠左室射血分数(EF)、缩短分数(FS)和左心室舒张末内径(LVEDD)、左心室收缩末内径(LVESD)、经右颈总动脉插管测定血压(BP)、左室舒张压(LVDP)和最大左室舒张压/收缩压变化速率(±LVdp/dtmax）。结果: 大鼠MI后心肌中TNF-α增加，Ins治疗可明显降低大鼠心肌中TNF-α的含量(P<0.05，n=6)。Ins治疗组大鼠EF、FS、LVDP和±LVdp/dtmax均明显高于对照组(P<0.05,n=10)，LVESD明显低于对照组(P<0.05，n=10)。与单独En治疗组相比，Ins+En治疗组大鼠EF、FS、LVDP和±LVdp/dtmax明显升高、LVESD明显降低(P<0.05，n=10)。结论: Ins可抑制MI后心室的扩张，改善心脏功能，但其机制不依赖于抑制心肌TNF-α的产生。

Effects of insulin on ventricular remodeling and cardiac functions after myocardial infarction and its underlying mechanism

AIM:To investigate the effect of insulin treatment on ventricular remodeling and cardiac functions after myocardial infarction (MI) and the underlying mechanism. METHODS: MI models were established by ligation of the left anterior descending coronary artery (LAD). Eighty male adult Sprague Dawley rats were randomly divided into five groups: sham (n=20), MI+saline (n=20), MI+insulin (n=20), MI+etanercept (n=10), and MI+etanercept+insulin (n=10). Serum and myocardial tumor necrosis factor-α (TNF-α) were measured at 1 week and 4 weeks after MI. Left ventricular (LV) fractional shortening (FS), ejection fraction (EF), LV end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) were measured with M-mode echocardiography. Catheters were inserted into the right carotid artery and then advanced into the LV to record the LV end-diastolic pressure (LVDP) and LV maximum rates of pressure development (±LV dp/dtmax). RESULTS: Myocardial TNF-α increased after MI and insulin administration significantly reduced myocardial TNF-α in post-MI rats (P<0.05, n=6). Moreover, EF, FS, LVDP and LVdp/dtmax increased and LVESD decreased in MI+insulin group compared with those in MI+saline group (all P<0.05, n=10). Compared with those in MI+etanercept group, EF, FS, LVDP and LVdp/dtmax increased and LVESD decreased in MI+insulin+etanercept group (all P<0.05, n=10). CONCLUSION: Insulin treatment alleviates left ventricular dilation and improves cardiac functions after MI in rats, but these effects may not be dependent on the inhibition of myocardial TNF-α.