冠心宁注射液通过CCL21调节心脏免疫改善心肌梗死作用  

Effect of Guanxinning injection on myocardial infarction by regulating cardiac immunity through CCL21

作　　者：白雨欣 张迎雪 石婷婷 朱思楠 许振坤 王虹[2] 陈璐[1] BAI Yu-xin;ZHANG Ying-xue;SHI Ting-ting;ZHU Si-nan;XU Zhen-kun;WANG Hong;CHEN Lu(Instrumental Analysis and Research Center,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;School of Medical Technology,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学测试中心,天津301617 [2]天津中医药大学医学技术学院,天津301617

出　　处：《中国药理学通报》2025年第5期960-969,共10页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82174205,82274135);天津市科技项目(No 23ZYJDSS00020,QN20230330)。

摘　　要：目的探讨冠心宁注射液调节心脏免疫微环境改善小鼠心肌梗死(myocardial infarction,MI)的作用机制。方法本研究采用永久性结扎冠状动脉左前降支制备小鼠MI模型,实验分为5组:假手术组、模型组、冠心宁注射液低剂量组,冠心宁注射液高剂量组、阳性药卡托普利组。对心脏称重,收集心脏组织采用Masson染色进行病理分析;免疫荧光染色检测梗死边缘区细胞凋亡及趋化因子配体21(C-C motif chemokine ligand 21,CCL21)的表达;流式细胞术检测心肌缺血组织及淋巴结中免疫细胞的比例;qRT-PCR检测心脏及体外人淋巴管内皮细胞(human lymphatic endothelial cells,HLEC)中CCL21的表达。结果模型组小鼠心脏明显肥大;与模型组比较,冠心宁注射液低剂量、高剂量组明显改善心脏肥大。冠心宁注射液低、高剂量组、卡托普利组MI边缘区细胞凋亡减少。与模型组相比,冠心宁注射液低、高剂量组梗死边缘区白细胞比例降低,调节心脏梗死边缘区及纵隔淋巴结CD4+T细胞、Treg细胞、CD8+T细胞比例;心脏及淋巴管分泌CCL21升高。结论冠心宁注射液可明显改善MI小鼠心脏肥大及纤维化,并减轻梗死边缘区细胞凋亡,且通过促进淋巴管中CCL21表达调节MI后纵隔淋巴结及心脏T细胞比例从而发挥抗心肌缺血损伤作用。Aim To investigate the mechanism of Guanxinning injection regulating cardiac immune microenvironment to improve myocardial infarction in mice.Methods In this study,MI model was established by permanent ligation of left anterior descending coronary artery in mice.The mice were divided into five groups:sham operation group,model group,Guanxinning injection low dose group,Guanxinning injection high dose group and positive drug captopril group.Hearts were weighed,heart tissues were collected,and Masson staining was used for pathological analysis of heart tissues;immunofluorescence staining was used to detect apoptosis and CCL21 expression in the infarct border zone;flow cytometry was used to detect the proportion of immune cells in myocardial ischemia tissues and lymph nodes;PCR was used to detect CCL21 expression in heart and in vitro human lymphatic endothelial cells(HLEC).Results Compared with the model group,the low and high dose groups of Guanxinning injection significantly improved cardiac hypertrophy.Apoptosis in the border zone of myocardial infarction was reduced in the low and high dose groups of Guanxinning injection and captopril group.Compared with the model group,the proportion of leukocytes in the infarct border zone was dreduced and the proportion of CD4+T cells,Treg cells,and CD8+T cells in the mediastinal lymph nodes and infarct border zone of the heart was regulated in the low and high dose groups of Guanxinning injection;CCL21 secretion by the heart and lymphatic vessels increased.Conclusions Guanxinning injection can significantly improve cardiac hypertrophy and fibrosis in MI mice,reduce apoptosis in the infarct border zone,and play a role in anti-myocardial ischemia injury by promoting CCL21 expression in lymphatic vessels to regulate the proportion of mediastinal lymph nodes and cardiac T cells after myocardial infarction.

关 键 词：冠心宁注射液 心肌梗死 免疫 趋化因子配体21 淋巴管 T细胞 

分 类 号：R-332[医药卫生] R282.71R322.26R331.125R392.12R542.22