Department of Anesthesiology, Beijing Jishuitan Hospital, Beijing, China.
Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1342-1349. doi: 10.26355/eurrev_201902_17029.
To investigate the effect of isoflurane on myocardial ischemia-reperfusion injury through the p38 mitogen-activated protein kinase (MAPK) signaling pathway.
A total of 36 specific-pathogen-free (SPF) Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12) and isoflurane group (n=12). In model group and isoflurane group, the myocardial ischemia-reperfusion injury model was established via the ligation of left anterior descending coronary artery (ischemia for 30 min and reperfusion for 3 h). In sham group, the left anterior descending coronary artery was not ligated, but the chest was opened and threaded using the same method. After ischemia, the rats in isoflurane group were inhaled with isoflurane. The cardiac function of rats in each group was detected before ischemia (T0) and once every 2 h after reperfusion (T1-T4) for a total of 5 times, and the cardiac function indexes included ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP). After the rats were executed, the myocardial infarction tissues were taken for hematoxylin-eosin (HE) staining and 2,3,5-triphenyltetrazolium chloride (TTC) staining to observe the morphological changes in tissues and the degrees of myocardial ischemia and infarction. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in myocardial cells in the infarction site in each group were detected using the MDA and SOD kits. Moreover, the expression levels of related proteins in the p38 MAPK signaling pathway in myocardial cells in the infarction site were detected via Western blotting.
In model group, the cardiac function was significantly damaged (p<0.01), there was significant pathological damage in the myocardium, the area of myocardial infarction was significantly increased (p<0.01), the MDA content was significantly increased (p<0.01), the SOD activity declined obviously (p<0.01), and the expression levels of p-p38 and p-tau protein were significantly increased (p<0.01) compared with those in control group. After intervention with isoflurane, the cardiac function of rats was significantly improved (p<0.01), the pathological damage in myocardial tissues was alleviated, the area of myocardial infarction was reduced (p<0.01), the MDA content declined (p<0.01), the SOD activity was increased (p<0.01), and the expression levels of p-p38 and p-tau protein were decreased (p<0.01).
Isoflurane can, through inhibiting the p38 MAPK signaling pathway, effectively protect the cardiac function of rats from myocardial ischemia-reperfusion injury, reduce the area of myocardial infarction, alleviate the pathological damage in myocardial cells and reduce the oxidative stress response.
通过丝裂原活化蛋白激酶（MAPK）信号通路研究异氟醚对心肌缺血再灌注损伤的影响。
36 只特定病原体（SPF）Sprague-Dawley 大鼠随机分为假手术组（n=12）、模型组（n=12）和异氟醚组（n=12）。在模型组和异氟醚组中，通过结扎左前降支冠状动脉（缺血 30 分钟，再灌注 3 小时）建立心肌缺血再灌注损伤模型。在假手术组中，不结扎左前降支冠状动脉，但采用相同方法打开胸部并穿线。缺血后，异氟醚组大鼠吸入异氟醚。各组大鼠在缺血前（T0）和再灌注后每 2 小时（T1-T4）共 5 次检测心功能，心功能指标包括射血分数（EF）、短轴缩短率（FS）、左室收缩压（LVSP）和左室舒张末期压（LVEDP）。处死大鼠后，取心肌梗死组织行苏木精-伊红（HE）染色和 2,3,5-三苯基氯化四氮唑（TTC）染色，观察组织形态变化及心肌缺血和梗死程度。采用 MDA 和 SOD 试剂盒检测各组梗死部位心肌细胞中丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性。此外，通过 Western blot 检测梗死部位心肌细胞中 p38 MAPK 信号通路相关蛋白的表达水平。
与对照组相比，模型组心功能明显受损（p<0.01），心肌病理损伤明显，心肌梗死面积明显增大（p<0.01），MDA 含量明显升高（p<0.01），SOD 活性明显降低（p<0.01），p-p38 和 p-tau 蛋白表达水平明显升高（p<0.01）。异氟醚干预后，大鼠心功能明显改善（p<0.01），心肌组织病理损伤减轻，心肌梗死面积缩小（p<0.01），MDA 含量降低（p<0.01），SOD 活性升高（p<0.01），p-p38 和 p-tau 蛋白表达水平降低（p<0.01）。
异氟醚通过抑制 p38 MAPK 信号通路，有效保护大鼠心肌缺血再灌注损伤的心功能，减少心肌梗死面积，减轻心肌细胞病理损伤，降低氧化应激反应。
