基于生物信息学和中性粒细胞胞外诱捕网效应探讨银杏叶提取物减轻心肌梗死后心肌损伤的机制  

Mechanism of Ginkgo biloba extract in alleviating myocardial injury after myocardial infarction:a bioinformatics and neutrophil extracellular trap study

作　　者：魏东升 刘雨婷 李涵[1,2] 齐佳杰 刘孝生 张哲[1,2,3] WEI Dongsheng;LIU Yuting;LI Han;QI Jiajie;LIU Xiaosheng;ZHANG Zhe(Graduate School,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Department of Geriatric,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110033,China)

机构地区：[1]辽宁中医药大学研究生院,沈阳110847 [2]辽宁中医药大学中医脏象理论及应用教育部重点实验室,沈阳110847 [3]辽宁中医药大学附属医院老年病科,沈阳110033

出　　处：《中国医科大学学报》2024年第10期870-876,共7页Journal of China Medical University

基　　金：国家中医药管理局青年岐黄学者支持项目(20201A2180)。

摘　　要：目的探讨银杏叶提取物减轻心肌梗死(MI)大鼠心肌损伤的机制。方法应用生物信息学挖掘银杏叶提取物治疗MI大鼠的关键靶点。采用冠状动脉结扎方法构建MI大鼠模型。采用随机数字法,将成模大鼠分为模型组、倍他乐克组(2.5 mg/kg)以及银杏叶提取物低(50 mg/kg)、中(100 mg/kg)、高(200 mg/kg)剂量组,另设假手术组。灌胃6周后,苏木精-伊红染色、天狼星红染色观察大鼠心肌组织病理变化;麦胚凝集素染色观察大鼠心肌细胞肥大情况;Western blotting检测MCODE核心靶点HIF1α、MAPK14、MMP9、CXCR4的表达变化。结果与假手术组比较,模型组大鼠心肌细胞排列不规则,出现明显炎症浸润,心肌组织Ⅰ型和Ⅲ型胶原纤维明显增多(P<0.05),MCODE核心靶点蛋白表达显著升高(P<0.05);与模型组比较,银杏叶提取物低、中、高剂量组大鼠心肌细胞间排列较紧密,炎症浸润减少,Ⅰ型和Ⅲ型胶原纤维明显减少(P<0.05),p-MAPK14、MMP9、CXCR4蛋白表达显著减少(P<0.05),HIF1α蛋白表达显著增加(P<0.05)。结论银杏叶提取物可能通过抑制中性粒细胞胞外诱捕网形成,发挥MI后心肌细胞保护作用。Objective To investigate the mechanism by which Ginkgo biloba extract reduces myocardial injury in rats with myocardial infarction(MI).Methods Bioinformatics was used to identify key targets of Ginkgo biloba extract in the treatment of MI in rats.An MI rat model was established via coronary artery ligation.Rats were randomly assigned to the model group,Betaloc ZOK group(2.5 mg/kg),and low-,medium-,and high-dose Ginkgo biloba extract groups(50,100,and 200 mg/kg,respectively).A sham-operation group was included for comparison.Following six weeks of gavage administration,myocardial tissues were examined using hematoxylin-eosin and Sirius red staining to assess pathological changes.Wheat germ agglutinin staining was used to observe cardiomyocyte hypertrophy.Western blotting was performed to evaluate changes in the expression of MCODE core targets,including HIF1α,MAPK14,MMP9,and CXCR4.Results Compared to the sham-operation group,the model group exhibited irregular arrangement of cardiomyocytes,significant inflammatory infiltration,and a marked increase in typeⅠandⅢcollagen fibers in the myocardial tissue(P<0.05).Additionally,significant upregulation in the expression of MCODE core target proteins(P<0.05)was observed.In contrast,compared to the model group,low-,medium-,and high-dose Ginkgo biloba extract groups displayed more orderly arrangement of cardiomyocytes,reduced inflammatory infiltration,significantly decreased levels of typeⅠandⅢcollagen fibers(P<0.05),notable downregulation in the expression of p-MAPK14,MMP9,and CXCR4 proteins(P<0.05),and significantly increased expression of HIF1αprotein(P<0.05).Conclusion Ginkgo biloba extract may exert protective effects on myocardial cells following MI by inhibiting the formation of neutrophil extracellular traps.

关 键 词：心肌梗死 银杏叶提取物 中性粒细胞胞外诱捕网 

分 类 号：R285.5[医药卫生—中药学]