天山花楸叶黄酮提取物抗心肌缺血再灌注损伤作用机理分析

Analysis of Anti-myocardial Ischemia-reperfusion Injury Mechanism of Flavonoids from Sorbus Tianshanensis Leaves

目的分析在抗心肌缺血再灌注损伤(MIRI)治疗中天山花楸叶黄酮提取物的作用机制。方法选取2020年1月—2021年1月实验室小鼠50只,全部样本实施K-H灌注液20 min灌注后,根据具体用药方法分组,对照组10只,另行110 min恒压灌注;模型组10只,20 min全心停灌+60 min复灌;高剂量FST组10只,K-H液20 min灌注+1.5 mg/L总黄酮10 min灌注,停灌20 min,K-H液复灌60 min;低剂量FST组10只,20 min K-H液灌注,0.5 mg/L金丝桃苷10 min灌注,停灌20 min,复灌60 minK-H液;CDZ组(抑制剂组)10只,K-H液20 min灌注,含抑制剂灌注液(1μmol/L)20 min灌注,停灌20 min,K-H液复灌60 min。借助网络药理学研究手段,研究天山花楸中对MIRI具有对抗作用的黄酮提取物,定位其作用靶点,分析作用机理。结果有效成分方面,天山花楸在抗心肌缺血再灌注损伤中发挥药效的成分以黄酮类化合物为主,在治疗时以TSPO为主要靶点,其中心血管相关靶标占比37%。剂量影响方面,不同剂量皆可改善患者心功能,修复心肌梗死组织,缓解病理损伤,提升心肌抗氧化水平,促进mPTP维持闭合状态,对线粒体水肿起到抑制作用。其中低剂量FST组心肌梗死面积(62.71±5.29)%,抑制剂组心肌梗死面积(50.24±4.80)%,高剂量用药药效较显著,心肌梗死面积为(46.19±4.58)%,消极影响较低,差异有统计学意义(F=51.403,P=0.017)。结论天山花楸叶黄酮提取物可用于修复MIRI,改善心肌梗死和心肌舒缩功能,降低相关组织氧化应激影响,药物成分在TSPO靶点发挥作用,阻断mPTP孔开放作用,缓解线粒体水肿,降低心肌损伤。

Objective To analyze the mechanism of flavonoid extracts from Sorbus tiansmanica leaves in the treatment of myocardial ischemia reperfusion injury(MIRI).Methods Fifty laboratory mice from January 2020 to January 2021 were selected.All samples were perfused with K-H infusion for 20 min,and then grouped according to specific medication methods.The control group(10 mice)was perfused for another 110 min at constant pressure.10 mice in model group were treated with 20 min whole-heart stop irrigation and 60 min reirrigation.In the high-dose FST group,10 rats were treated with K-H solution for 20 min+1.5 mg/L total flavonoids for 10 min,then stopped for 20 min,followed by K-H solution reperfusion for 60 min.Ten rats in low-dose FST group were perfused with K-H solution for 20 min,followed by 0.5 mg/L hyperoside for 10 min,stopped for 20 min,and reperfusion with K-H solution for 60 min.10 rats in CDZ group(inhibitor group)were perfused with K-H solution for 20 min,including inhibitor infusion(1μmol/L)for 20 min,stopped for 20 min,and then re-perfused with K-H solution for 60 min.Using network pharmacological research methods,the flavonoids extracts of Sorbus tiansmanica with anti-MIRI effect were studied,the target of action was identified,and the mechanism of action was analyzed.Results In terms of active ingredients,Sorbus Tianshanensis plays a major role in anti-myocardial ischemia-reperfusion injury.Flavonoids were the main ingredients,and TSPO was the main target for treatment,of which cardiovascular-related targets account for 37%.In terms of dose impact,different doses could improve the patient's heart function,repair myocardial infarction tissue,relieve pathological damage,increase myocardial antioxidant level,promote mPTP to maintain a closed state,and inhibit mitochondrial edema.Among them,the area of myocardial infarction in the low-dose FST group was(62.71±5.29)%,and the area of myocardial infarction in the inhibitor group was(50.24±4.80)%.The high-dose medication was more effective,and the area of myocardial infarction was(46.19±4.58)%,the negative impact was low,the difference was statistically significant(F=51.403,P=0.017).Conclusion The flavonoid extract of Sorbus tianshanensis leaf can be used to repair MIRI,improve myocardial infarction and myocardial systolic and contraction function,and reduce the impact of oxidative stress in related tissues.The drug components play a role in the TSPO target and block the opening of mPTP pores,relieve mitochondrial edema and reduce myocardial damage.