探讨艾司洛尔对脓毒症大鼠急性心肌损伤的保护作用及其作用机制。

将26只成年雄性Sprague-Dawley大鼠按随机数字表法分为假手术组（6只）、模型组（10只）和艾司洛尔组（10只），各组分别保证6只大鼠进行后续实验分析。艾司洛尔组大鼠持续经左颈内静脉泵入艾司洛尔注射液（15 mg·kg^-1·h^-1）；假手术组、模型组持续泵入等量等渗NaCl溶液。注射30 min后模型组和艾司洛尔组大鼠采用腹腔注射脂多糖（10 mg/kg）建立脓毒症急性心肌损伤模型；假手术组注射等量等渗NaCl溶液。模型构建成功24 h后，观察各组大鼠死亡情况；腹主动脉采血，检测血清心肌肌钙蛋白I（cTnI）水平；取血后处死大鼠，取心脏组织行苏木素-伊红染色，光镜下观察心脏组织病理学变化，并采用Western-blotting检测Beclin-1、微管相关蛋白1轻链3-Ⅱ（LC3-Ⅱ）及Parkin蛋白的表达水平。

建模后24 h假手术组大鼠无死亡，模型组大鼠死亡4只，艾司洛尔组大鼠死亡2只。光镜下，假手术组大鼠心肌组织结构完整，心肌纤维排列有序，心肌细胞形态正常；模型组大鼠心肌纤维紊乱，炎症细胞浸润，细胞肿胀明显，组织坏死；艾司洛尔组大鼠心肌纤维较规则，炎症细胞浸润减少，心肌细胞肿胀好转。3组大鼠间血清cTnI、Beclin-1、LC3-Ⅱ及Parkin蛋白表达水平比较，差异均有统计学意义（F=17.300、110.000、57.670、14.980；P均<0.001）。与模型组大鼠比较，假手术组及艾司洛尔组大鼠血清cTnI均明显降低[（3.2 ± 0.8）、（1.4 ± 0.6）、（1.4 ± 0.7）ng/L]，Beclin-1[（0.21 ± 0.07）、（1.01 ± 0.13）、（0.98 ± 0.11）]、LC3-Ⅱ[（0.29 ± 0.11）、（1.02 ± 0.16）、（0.99 ± 0.13）]及Parkin[（0.73 ± 0.09）、（1.00 ± 0.13）、（1.13 ± 0.16）]蛋白表达水平均明显升高（P均<0.05）。

艾司洛尔对脓毒症大鼠急性心肌损伤有显著的保护作用，其具体机制与促进Parkin介导的线粒体自噬有关。

To investigate the protective effect and specific mechanism of esmolol on sepsis-induced acute cardiac injury in rats.

A total of 26 adult male Sprague-Dawley rats were randomly divided into the sham group (6 rats), sepsis group (10 rats) and esmolol group (10 rats), and 6 rats in each group were guaranteed for follow-up experimental analysis. In the esmolol group, esmolol (15 mg·kg^-1·h^-1) was continuously pumped through the left internal jugular vein, and the same amount of isotonic NaCl solution was continuously pumped into the sham group and sepsis group. After 30 min of injection, the sepsis-induced acute cardiac injury model was reproduced by intraperitoneal injection of lipopolysaccharide (10 mg/kg) in the sepsis group and esmolol group, and rats in the sham group only received an equivalent amount of isotonic NaCl solution. The death of rats in each group was observed at 24 h after modeling, and the abdominal aorta blood was collected to test the serum cardiac troponin I (cTnI). The rats were sacrificed after blood collection. The cardiac tissues were collected to observe the pathological structure changes under the hematoxylin-eosin staining by light microscope, and the expression levels of Beclin-1, microtubule-associated protein 1 light 3-Ⅱ (LC3-Ⅱ) and Parkin proteins were tested by Western-blotting.

There were no deaths in the sham group, 4 in the sepsis group and 2 in the esmolol group at 24 h after modeling. Under light microscope, in the sham group, the myocardium structure was complete, the myocardium fibers were arranged in order, and the morphology of myocardium cells was normal; in the sepsis group, myocardial fibers were disordered, inflammatory cells infiltrated, cell swelling was obvious, and tissue necrosis was observed; in the esmolol group, the myocardial fibers were relatively regular, the infiltration of inflammatory cells reduced, and the swelling of myocardial cells improved. The levels of cTnI, Beclin-1, LC3-Ⅱ and Parkin proteins among the three groups all showed significant differences (F = 17.300, 110.00, 57.670, 14.980; all P < 0.001). Compared with the sepsis group, the level of cTnI was much lower [(3.2 ± 0.8), (1.4 ± 0.6), (1.4 ± 0.7) ng/L], and the levels of Beclin-1 [(0.21 ± 0.07), (1.01 ± 0.13), (0.98 ± 0.11)], LC3-Ⅱ [(0.29 ± 0.11), (1.02 ± 0.16), (0.99 ± 0.13)] and Parkin [(0.73 ± 0.09), (1.00 ± 0.13), (1.13 ± 0.16)] proteins were much higher in the sham group and esmolol group (all P < 0.05).

Esmolol has a significant protective effect on acute myocardial injury in sepsis rats, and its mechanism is related to the promotion of Parkin-mediated mitochondrial autophagy.