■心肌缺血/再灌注(I/R)损伤是经皮冠状动脉介入治疗的主要障碍,在临床上缺乏有效的治疗措施。Siegesbeckiae(HS)是一种具有多种药理活性和心血管保护作用的传统草药。然而,关于HS在心脏I/R中的作用的数据很少。本研究旨在探讨HS水提物对心脏I/R损伤的作用及其机制。
■制备Siegesbeckiae水提取物并通过UHPLC-MS/MS进行分析。每天一次连续7天胃内给药HS后,雄性Sprague-Dawley大鼠接受左前降支冠状动脉30分钟闭塞,然后再灌注120分钟以引发I/R。各种参数,如心肌梗死和细胞凋亡,12导联心电图和血流动力学,心脏形态学和心肌酶,定量蛋白质组学,线粒体超微结构和电子传递链(ETC)功能,氧化应激和抗氧化,和NLRP3炎性体和炎症进行评估。
■HS水提物的化学成分主要分为黄酮类化合物,二萜,有机酸。在体内,HS水提取物显著减轻心肌I/R损伤,正如梗死面积减少所证明的那样,凋亡细胞,和心脏损伤酶;ST段抬高下降;改善心功能;并保留形态。定量蛋白质组学表明,HS逆转了Adgb表达的改变,Cbr1,Decr1,Eif5,Uchl5,Lmo7,Bdh1,Ckmt2,COX7A,I/R后的RT1-CE1此外,暴露于I/R后,HS保留了心肌超微结构并恢复了线粒体ETC复合物的功能;HS显着抑制I/R引起的ROS增加,RNS,MDA,和8-OHdG,抑制MnSOD的乙酰化,并恢复了MnSOD的活性;HS逆转了I/R诱导的NLRP3炎症小体的升高,抑制了炎症因子的释放和细胞凋亡。
■Siegesbeckiae水提取物改善心脏I/R损伤,这与减轻氧化应激有关,抑制NLRP3炎性体,通过调节Adgb的表达来恢复线粒体功能,Cbr1,Decr1,Eif5,Uchl5,Lmo7,Bdh1,Ckmt2,COX7A,和RT1-CE1。
UNASSIGNED: Myocardial ischemia/reperfusion (I/R) injury is the main obstacle to percutaneous coronary intervention, lacking effective therapeutic measures in a clinical setting. Herba Siegesbeckiae (HS) is a traditional herb with multiple pharmacological activities and evidence of cardiovascular protection. However, few data are available regarding the role of HS in cardiac I/R. This study aimed to explore the effect and underlying mechanism of HS aqueous extract on cardiac I/R injury.
UNASSIGNED: Herba Siegesbeckiae aqueous extract was prepared and analyzed by UHPLC-MS/MS. After intragastric administration of HS once daily for 7 days, male Sprague-Dawley rats were subjected to 30 min occlusion of the left anterior descending coronary artery followed by 120 min reperfusion to elicit I/R. Various parameters like myocardial infarction and apoptosis, 12-lead ECG and hemodynamics, cardiac morphology and myocardial enzymes, quantitative proteomics, mitochondrial ultrastructure and electron transport chain (ETC) function, oxidative stress and antioxidation, and NLRP3 inflammasome and inflammation were evaluated.
UNASSIGNED: The chemical constituents of HS aqueous extract were mainly divided into flavonoids, diterpenoids, and organic acids. In vivo, HS aqueous extract notably alleviated myocardial I/R injury, as evidenced by a reduction in infarct size, apoptotic cells, and cardiac lesion enzymes; decline of ST-segment elevation; improvement of cardiac function; and preservation of morphology. Quantitative proteomics demonstrated that HS reversed the alteration in the expression of Adgb, Cbr1, Decr1, Eif5, Uchl5, Lmo7, Bdh1, Ckmt2, COX7A, and RT1-CE1 after I/R. In addition, HS preserved myocardial ultrastructure and restored the function of mitochondrial ETC complexes following exposure to I/R; HS significantly suppressed I/R-elicited increase of ROS, RNS, MDA, and 8-OHdG, restrained the acetylation of MnSOD, and recovered the activity of MnSOD; and HS reversed I/R-induced elevation of NLRP3 inflammasome and inhibited the release of inflammatory factors and pyroptosis.
UNASSIGNED: Herba Siegesbeckiae aqueous extract ameliorated cardiac I/R injury, which is associated with mitigating oxidative stress, suppressing NLRP3 inflammasome, and restoring mitochondrial function by regulating the expression of Adgb, Cbr1, Decr1, Eif5, Uchl5, Lmo7, Bdh1, Ckmt2, COX7A, and RT1-CE1.