目的 探究艾片基于“开窍通络”改善冠脉微循环障碍（coronary microcirculation disorders，CMD）大鼠的作用及可能机制。方法 选取雄性SD大鼠48只，随机分为假手术组、模型组和艾片低、高剂量组（0.05、0.10 g/kg），除假手术组注射等量PBS外，其余组大鼠经左心室注射聚乙烯微球混悬液构建CMD大鼠模型。观察中医证候宏观评价指标舌象；检测血流动力学中CMD大鼠血流量（mean blood flow，MBF）、动脉平均压（mean arterial pressure，MAP）及左心室压变化；检测血液流变学中血液黏度、凝血四项、血小板功能指标的异常变化情况；生化分析仪及试剂盒检测大鼠血清中心功能、内皮功能及能量代谢相关指标含量变化；苏木素-伊红（hematoxylin-eosin，HE）染色观察心肌组织病变情况；通过可视化技术结合Angio Tool软件及泊肃叶公式分析冠脉微血管面积、密度、直径、空隙度及血流阻力；Western blotting检测心肌组织中能量代谢相关蛋白肝激酶B1（liver kinase B1，LKB1）、腺苷酸活化蛋白激酶（AMP-activated protein kinase，AMPK）、磷酸化腺苷酸活化蛋白激酶（phospho-AMPK，p-AMPK）、过氧化物酶体增殖物激活受体γ辅激活酶因子-1a（peroxisome proliferators-activated receptor γ coactivator-1 alpha，PGC-1a）及血管新生相关蛋白血管内皮生长因子（vascular endothelial growth factor，VEGF）、血管内皮细胞生长因子受体2（vascular endothelial growth factor receptor 2，VEGFR2）蛋白表达情况。结果 与假手术组比较，艾片可显著升高CMD大鼠MBF、MAP（P＜0.01、0.05），改善左心室压异常现象；显著降低CMD大鼠平均血小板体积（mean platelet volume，MPV），升高血小板计数（platelet count，PLT），显著延长凝血酶原时间（prothrombin time，PT）及活化部分凝血酶原时间（activated partial thromboplastin time，APTT），改善CMD大鼠血液流变学异常情况（P＜0.05、0.01）；显著降低血清中肌酸激酶（creatine kinase，CK）、肌酸激酶同工酶（creatine kinase MB，CK-MB）、乳酸脱氢酶（lactate dehydrogenase，LDH）、天门冬氨酸氨基转移酶（aspartic transaminase，AST）、葡萄糖（glucose，GLU）、内皮素-1（endothelin-1，ET-1）含量（P＜0.05、0.01），升高血清中一氧化氮（nitric oxide，NO）和心肌组织中腺嘌呤核苷三磷酸（adenosine Triphosphate，ATP）含量（P＜0.05、0.01），改善内皮功能受损及能量代谢紊乱情况；显著改善CMD大鼠微血管密度、直径及面积降低，空隙度和血流阻力升高的情况（P＜0.01）；Western blotting结果显示艾片能显著升高CMD大鼠心肌组织LKB1、p-AMPK/AMPK、PGC-1a、VEGF、VEGFR2蛋白水平表达（P＜0.05、0.01）。结论 艾片可能通过改善CMD大鼠心肌能量代谢异常情况，促进血管新生、纠正血管舒缩障碍达到“开窍通络”的作用，为治疗CMD提供新思路。

Objective To investigate the effects and possible mechanisms of Blumea balsamifera in improving coronary microcirculation disorders (CMD) in rats based on “Kaiqiao Tongluo”.Methods A total of 48 male SD rats were selected and randomly divided into sham group, model group, low- and high-dose group of B. balsamifera (0.05, 0.10 g/kg). Except for the sham group, which was injected with an equal amount of PBS, the other three groups were injected with polyethylene microsphere suspension into the left ventricle to prepare CMD rat models. Observing the tongue image, a macroscopic evaluation index of traditional Chinese medicine evidence, detecting the changes of mean blood flow (MBF), mean arterial pressure (MAP) and left ventricular pressure in CMD rats in hemodynamics, detecting the abnormal changes of blood viscosity, coagulation four items, and platelet function indexes in blood rheology, and the changes of the content of serum central function, endothelial function, and energy metabolism-related indexes were detected by biochemical analyzers and kits. Hematoxylin-eosin (HE) staining was used to observe myocardial tissue lesions, coronary microvessel area, density, diameter, voidness, and resistance to blood flow were analyzed by visualization technology combined with Angio Tool software and Poisson Leaf formula, and energy metabolism-related proteins liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), peroxisome proliferators-activated receptor γ coactivator-1 alpha (PGC-1a), and vascular neovascularization-related proteins vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) protein expression were detected byWestern blotting. Results Compared with the sham surgery group, B. balsamifera significantly increased MBF and MAP in CMD rats (P < 0.05, 0.01), and improved abnormal left ventricular pressure; significantly reduced mean platelet volume (MPV) and increased platelet count (PLT) in CMD rats, significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), and improved abnormal hemorheology in CMD rats (P < 0.05, 0.01); significantly reduced the levels of creatine kinase (CK), creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), glucose (GLU), and endothelin-1 (ET-1) in serum (P < 0.05, 0.01), increased the levels of nitric oxide (NO) in serum and adenosine triphosphate (ATP) in myocardial tissue (P < 0.05, 0.01), and improved endothelial function impairment and energy metabolism disorders; significantly improved decreased microvessel density, diameter and area, and elevated voidness and resistance to blood flow in CMD rats (P < 0.01). The Western blotting results showed that B. balsamifera significantly increased the protein levels of LKB1, p-AMPK/AMPK, PGC-1α, VEGF, and VEGFR2 in the myocardial tissue of CMD rats (P < 0.05, 0.01). Conclusion B. balsamifera may improve the abnormal myocardial energy metabolism in CMD rats, promote angiogenesis, and correct vascular constriction disorders to achieve the “Kaiqiao Tongluo” effect, providing new ideas for treating CMD.

R285.5

江西省自然科学基金重点项目（20224ACB206043）;国家自然科学基金项目（82160732）;国家重点研发计划项目（2018YFC1706102）;中药药效物质基础江西省重点实验室项目（2024SSY07102）