DataSheet_1_Shenlian Extract Against Myocardial Injury Induced by Ischemia Through the Regulation of NF-κB/IκB Signaling Axis.pdf

Ischemic heart disease (IHD), caused predominantly by atherosclerosis, is a leading cause of global mortality. Our previous studies showed that Shenlian extract (SL) could prevent the formation of atherosclerosis and enhance the stability of atherosclerotic plaques. To further investigate the protective effects of SL on myocardial ischemic injury and its possible mechanisms, anesthetized dogs, ex vivo rat hearts, and H9c2 cardiomyocytes were used as models. The results showed that SL had a significant protective effect on the anesthetized dog ligating coronary artery model, reduced the degree of myocardial ischemia (Σ-ST), and reduced the scope of myocardial ischemia (N-ST). Meanwhile, SL alleviated ischemic reperfusion damage in ex vivo rat hearts with improved LVEDP and ± dp/dtmax values of the left ventricle. SL reduced the pathological changes of LDH, IL-1β, MDA, and NO contents, all of which are related to the expression of NF-κB. Further analysis by Bio-Plex array and signal pathway blocker revealed that the phosphorylation of IκB was a key factor for SL to inhibit myocardial ischemic injury, and the regulation of SL on IκB was primarily related to degradation of the IκB protein. These results provided dependable evidence that SL could protect against myocardial ischemic injury through the NF-κB signaling pathway.

以动脉粥样硬化（atherosclerosis）为主要致病因素的缺血性心脏病（Ischemic Heart Disease, IHD）是全球范围内的首要致死病因之一。本团队前期研究证实，参莲提取物（Shenlian Extract, SL）可抑制动脉粥样硬化斑块形成，并提升斑块稳定性。为进一步探究参莲提取物对心肌缺血损伤的保护作用及其潜在分子机制，本研究采用麻醉犬、离体大鼠心脏及H9c2心肌细胞作为实验模型。研究结果显示，参莲提取物对冠状动脉结扎麻醉犬模型具有显著保护作用，可降低心肌缺血程度（Σ-ST）并缩小缺血范围（N-ST）。与此同时，参莲提取物可缓解离体大鼠心脏的缺血再灌注损伤，改善左心室舒张末期压（left ventricular end-diastolic pressure, LVEDP）及左心室±dp/dtmax指标。参莲提取物可降低乳酸脱氢酶（lactate dehydrogenase, LDH）、白细胞介素-1β（interleukin-1β, IL-1β）、丙二醛（malondialdehyde, MDA）及一氧化氮（nitric oxide, NO）的病理异常水平，上述指标均与核因子κB（nuclear factor-κB, NF-κB）的表达调控相关。通过Bio-Plex悬浮芯片技术（Bio-Plex array）及信号通路阻断剂开展的进一步分析显示，IκB（inhibitor of nuclear factor kappa-B）的磷酸化是参莲提取物抑制心肌缺血损伤的关键环节，且参莲提取物对IκB的调控主要与其介导IκB蛋白降解有关。上述研究结果为参莲提取物通过核因子κB（NF-κB）信号通路发挥心肌缺血损伤保护作用提供了可靠的实验依据。