作者：王青伟，李悦，刘强，刘业发，夏昆，丁荣晶

单位：

1.100044北京市，北京大学人民医院心脏中心 2.100085北京市，急性心肌梗死早期预警和干预北京市重点实验室 3.101199北京市，北京市结核病胸部肿瘤研究所 4.100069北京市，首都医科大学附属北京朝阳医院心脏中心 通信作者：丁荣晶，E-mail：drj2003@vip.163.com

单位（英文）：

1.Heart Center, Peking University People's Hospital, Beijing 100044, China 2.Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Beijing 100085, China 3.Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101199, China 4.Heart Center, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing 100069, China Corresponding author: DING Rongjing, E-mail：drj2003@vip.163.com

关键词：

心肌梗死; 急性心肌梗死; 1,6-二磷酸果糖口服液; 细胞凋亡; 氧化应激; 能量代谢;

关键词（英文）：

Myocardial infarction; Acute myocardial infarction; Fructose-1, 6-diphosphate oral liquid; Cell apoptosis;Oxidative stress; Energy metabolism

中图分类号：

DOI：

10.12114/j.issn.1008-5971.2022.00.124

基金项目：

国家自然科学基金资助项目（81772446）

摘要：

目的 探讨1,6-二磷酸果糖（FDP）口服液对急性心肌梗死（AMI）大鼠心肌细胞凋亡、氧化应激和能量代谢的影响及可能机制。方法 本实验时间为2020年12月—2021年6月。选取SPF级雄性SD大鼠20只，结扎左前降支构建AMI模型，将建模成功后存活24 h的12只大鼠随机分成模型组、FDP组，每组6只。FDP组大鼠给予FDP口服液灌胃21 d，模型组大鼠给予0.9%氯化钠溶液灌胃21 d。采用HE染色检测心肌组织形态学特征，Masson染色检测心肌组织纤维化程度、心肌胶原面积，TUNEL染色检测心肌细胞凋亡率，比色法检测心肌组织中ATP、超氧化物歧化酶（SOD）、丙二醛（MDA）含量，Western blotting法检测心肌组织中磷脂酰肌醇-3-激酶（PI3K）、磷酸化蛋白激酶B(p-AKT)蛋白表达水平。结果 HE染色结果显示，模型组大鼠心肌纤维排列紊乱，体积增大，间隙变宽；FDP组大鼠大部分心肌纤维排列较为整齐，间隙较为清晰，保持了心肌组织相对正常的结构和形态。光镜下，模型组大鼠心肌组织纤维化明显，可见岛状存活的心肌细胞；FDP组大鼠心肌梗死程度明显减轻，存活的心肌细胞增多，且与模型组大鼠相比，其心肌组织纤维化面积明显缩小。FDP组大鼠心肌胶原面积、心肌细胞凋亡率低于模型组（P<0.05）。FDP组大鼠心肌组织中ATP、SOD含量高于模型组，心肌组织中MDA含量低于模型组（P<0.05）。FDP组大鼠心肌组织中PI3K、p-AKT蛋白表达水平高于模型组（P<0.001）。结论 FDP口服液可抑制AMI大鼠心肌纤维化、心肌细胞凋亡、氧化应激，改善能量代谢，其机制可能与PI3K/AKT信号通路激活相关，这为减轻急性心肌缺血缺氧损伤和心肌保护提供了新的思路。

英文摘要：

【Abstract】　Objective To investigate the effects of fructose 1, 6-diphosphate (FDP) oral liquid on myocardialapoptosis, oxidative stress and energy metabolism in rats with acute myocardial infarction (AMI) and its possible mechanism.MethodsThe experimental time was December 2020 to June 2021. Twenty SPF male SD rats were selected, and the left anteriordescending branch was ligated to construct the AMI model. The 12 rats that survived for 24 hours after successful modeling wererandomly divided into model group and FDP group, with 6 rats in each group. Rats in FDP group were given FDP oral solution bygavage for 21 days, and rats in model group were given 0.9% sodium chloride solution by gavage for 21 days. HE staining was usedto detect the morphological characteristics of myocardial tissue, Masson staining was used to detect degree of myocardial fibrosisand the area of myocardial collagen, TUNEL staining was used to detect the apoptosis rate of myocardial cells. The contents ofATP, superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue were determined by colorimetric method. Theprotein expression levels of phosphatidylinositol-3-kinase (PI3K) and phosphorylated protein kinase B (p-AKT) were detected byWestern blotting method. Results HE staining showed that the myocardial fibers in the model group were disordered, the volumeincreased and the gap widened; most of the myocardial fibers in FDP group were arranged in order and the gap was clear, whichmaintained the relatively normal structure and morphology of myocardial tissue. Under light microscope, myocardial fibrosis wasobvious in the model group, and island viable cardiomyocytes were seen; the degree of myocardial infarction in FDP group wassignificantly reduced, the number of viable cardiomyocytes increased, and the area of myocardial fibrosis was significantly reducedcompared with that in model group. The myocardial collagen area and cardiomyocyte apoptosis rate in FDP group were lower thanthose in model group (P <0.05) . The contents of ATP and SOD in myocardial tissue of FDP group were higher than those of modelgroup, and the content of MDA in myocardial tissue was lower than that of model group (P <0.05) . The expression levels of PI3Kand p-AKT protein in myocardial tissue of FDP group were higher than those of model group (P <0.001) .Conclusion FDP oralliquid can inhibit myocardial fibrosis, cardiomyocyte apoptosis, oxidative stress and improve energy metabolism in AMI rats. Itsmechanism may be related to the activation of PI3K/AKT signal pathway, which provides a new idea for reducing acute myocardialischemia and hypoxia injury and myocardial protection.

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