Qin Zhuyun, Shen Shixuan, Qu Kaiyong, Nie Yu, Zhang Haitao
State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Fuwai Hospital, Beijing, China.
Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China.
J Cell Mol Med. 2021 May 31;25(13):6448-54. doi: 10.1111/jcmm.16649.
Myocardial ischemia-reperfusion injury (MIRI) with concurrent severe sepsis has led to substantial mortality. Mild hypothermia (MHT) has been proved to have a therapeutic effect in either MIRI or severe sepsis, which suggests it might be beneficial for MIRI complicating severe sepsis. In this study, Sprague-Dawley rats with MIRI complicating severe sepsis were allotted in either MHT (33 ± 0.5°C) group or normothermia (NT, 37 ± 0.5°C) group; as control, rats receiving sham surgery and normal saline were kept at NT. After 2h of temperature maintenance, blood and heart tissue were acquired for detections. Lactate dehydrogenase (LDH) and MB isoenzyme of creatine kinase (CK-MB) in blood, triphenyl tetrazolium chloride and Evans blue staining, hematoxylin and eosin staining for myocardium were employed to detect myocardial damage. Tumor necrosis factor (TNF)-α and caspase-3 was performed by immunohistochemistry to exam myocardial inflammation and apoptosis. Detection of NADPH oxidase (NOX) 2 was for myocardial oxidative stress. In MHT group, systolic blood pressure was improved significantly compared with NT group. Myocardial infarct size, morphological change, LDH and CK-MB levels were attenuated compared to NT group. Moreover, less expressions of TNF-α, caspase-3 and NOX2 in MHT group were presented compared with NT group. MHT showed cardioprotection by improving cardiac dysfunction, reducing myocardial infarct size and attenuating myocardial injury, inflammation, apoptosis and oxidative stress.
合并严重脓毒症的心肌缺血再灌注损伤（MIRI）已导致大量死亡。低温治疗（MHT）已被证明对MIRI或严重脓毒症均有治疗作用，这表明其可能对并发严重脓毒症的MIRI有益。在本研究中，将并发严重脓毒症的MIRI的Sprague-Dawley大鼠分为MHT组（33 ± 0.5°C）或正常体温组（NT，37 ± 0.5°C）；作为对照，接受假手术和生理盐水的大鼠维持在正常体温。维持体温2小时后，采集血液和心脏组织进行检测。采用血液中的乳酸脱氢酶（LDH）和肌酸激酶MB同工酶（CK-MB）、氯化三苯基四氮唑和伊文思蓝染色、心肌苏木精和伊红染色来检测心肌损伤。通过免疫组织化学检测肿瘤坏死因子（TNF）-α和半胱天冬酶-3以检查心肌炎症和细胞凋亡。检测NADPH氧化酶（NOX）2以评估心肌氧化应激。与NT组相比，MHT组的收缩压显著改善。与NT组相比，MHT组的心肌梗死面积、形态变化、LDH和CK-MB水平均减轻。此外，与NT组相比，MHT组中TNF-α、半胱天冬酶-3和NOX2的表达较少。MHT通过改善心脏功能障碍、减小心肌梗死面积以及减轻心肌损伤、炎症、细胞凋亡和氧化应激发挥心脏保护作用。
