血脂康通过PI3K/Akt/eNOS通路防治冠状动脉微循环障碍疾病  

Prevention and Treatment of Coronary Microvascular Dysfunction by Xuezhikang through PI3K/Akt/eNOS Pathway

作　　者：黄日康 张丽媛 臧子叶 梁五林 张明倩 成璐 高佳慧 谭琪玲 黄芷珊 葛东宇 张硕峰[1] HUANG Rikang;ZHANG Liyuan;ZANG Ziye;LIANG Wulin;ZHANG Mingqian;CHENG Lu;GAO Jiahui;TAN Qiling;HUANG Zhishan;GE Dongyu;ZHANG Shuofeng(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]北京中医药大学中医学院,北京102488

出　　处：《中国现代中药》2025年第2期282-295,共14页Modern Chinese Medicine

基　　金：北京市自然科学基金项目(7144222)。

摘　　要：目的:探索血脂康预防治疗冠状动脉微循环障碍(CMVD)的药效与机制,为临床用药提供依据。方法:基于网络药理学方法,通过文献记载及多个数据库筛查分析,对交集靶点进行富集分析。随后使用高血脂合并月桂酸钠注射法制备CMVD大鼠模型,检测氧化应激、炎症反应、内皮功能、组织形态变化,以及预测通路上相关蛋白质表达,研究血脂康防治CMVD的疗效,验证其机制。结果:网络药理学分析得到血脂康治疗CMVD的223个交集靶点,并筛选出43个关键靶点,这些靶点涉及蛋白质磷酸化、丝裂原活化蛋白激酶(MAPK)正向调节,调节炎症反应等方面,聚类分析发现通路主要聚集于心肌损伤通路[磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)通路]。动物实验表明,血脂康可以降低心肌损伤标志物心肌肌钙蛋白Ⅰ(cTn-Ⅰ)、肌酸激酶-心肌带(CK-MB)和1型乳酸脱氢酶(LDH 1)水平,有效改善血清丙二醛(MDA)、超氧化物歧化酶(SOD)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6水平异常情况,纠正CMVD大鼠体内血管内皮调节代谢物一氧化氮(NO)与内皮素-1(ET-1)异常现象,减少CMVD大鼠血栓素B2(TXB2)与血管性血友病因子(vWF)产生,抑制血小板凝聚。组织形态学观察结果表明,血脂康可以减轻心肌缺血坏死面积,减少血栓形成。蛋白质免疫印迹法结果显示,血脂康可显著促进PI3K与Akt活化并明显促进内皮型一氧化氮合酶(eNOS)蛋白质表达。结论:血脂康可有效预防CMVD导致的内皮功能障碍与心肌损伤,其机制与活化PI3K/Akt/eNOS通路,进而促进NO生成、维持血管内皮功能、抑制血栓形成有关。Objective:This study aims to explore the efficacy and mechanisms of Xuezhikang(XZK)in preventing and treating coronary microvascular dysfunction(CMVD),so as to provide evidence for clinical application.Methods:Based on network pharmacology,literature records,and multi-database screening,enrichment analysis was performed on intersection targets.A rat model of CMVD was established by using hyperlipidemia combined with sodium laurate injection.Oxidative stress,inflammatory response,endothelial function,morphological changes in tissue,and expression of relevant proteins in predicted pathways were detected to study the efficacy of XZK in preventing and treating CMVD and verify its mechanism.Results:Network pharmacology analysis identified 43 key targets of XZK in preventing and treating CMVD,as well as 223 intersection targets of components and diseases,which were involved in protein phosphorylation,positive regulation of mitogen-activated protein kinase(MAPK),and regulation of inflammatory responses.Clustering analysis revealed that the pathways were mainly concentrated in the myocardial injury pathway(phosphatidylinositol 3-kinase/protein kinase B,PI3K/Akt pathway).Animal experiments showed that XZK could reduce myocardial injury markers such as cardiac troponinⅠ(cTn-Ⅰ),creatine kinase-myocardial band(CK-MB),and lactate dehydrogenase 1(LDH 1).It effectively improved abnormal serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6).It also corrected the abnormalities in endothelial regulatory metabolites,nitric oxide(NO),and endothelin-1(ET-1),reduced the production of thromboxane B2(TXB2)and von Willebrand factor(vWF),and inhibited platelet aggregation in CMVD rats.Histological observations indicated that XZK could reduce the area of myocardial ischemic necrosis and decrease thrombus formation.Western blot(WB)results showed that XZK significantly promoted the activation of PI3K and Akt and markedly enhanced the expression o

关 键 词：冠状动脉微循环障碍 血脂康 网络药理学 磷脂酰肌醇3-激酶/蛋白激酶B/内皮型一氧化氮合酶通路 内皮功能 

分 类 号：R285[医药卫生—中药学]