冠心宁注射液促进淋巴管新生改善心肌缺血损伤作用的研究  

Effect of Guanxinning Injection in improving lymphangiogenesis to relieve myocardial ischemia injury

作　　者：张迎雪 朱思楠 房志锐 许振坤 白雨欣 王虹[2] 陈璐[1] Zhang Yingxue;Zhu Sinan;Fang Zhirui;Xu Zhenkun;Bai Yuxin;Wang Hong;Chen Lu(Instrumental Analysis and Research Center,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;不详)

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：《中国循证心血管医学杂志》2025年第2期175-179,共5页Chinese Journal of Evidence-Based Cardiovascular Medicine

基　　金：国家自然科学基金资助项目(82174205);国家自然科学基金资助项目(82274135)。

摘　　要：目的探讨冠心宁注射液促进淋巴管新生改善小鼠心肌梗死(MI)后心室重构的作用机制。方法将100只6~8周龄健康C57BL/6雄性小鼠随机分为假手术组、MI模型组、冠心宁注射液低剂量组、冠心宁注射液高剂量组、卡托普利组,每组各20只。除假手术组外,其余组通过永久性结扎冠状动脉左前降支制备小鼠MI模型。假手术组及MI模型组腹腔注射0.1 ml生理盐水,冠心宁注射液低、高剂量组腹腔分别注射2.5 ml/kg及5 ml/kg冠心宁注射液、卡托普利组灌胃给药23.4 ml/kg卡托普利,术后每天给药1次,连续给药28 d。治疗4周后,超声心动图检测各组小鼠左室射血分数(LVEF)、左室短轴缩短率(LVFS)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD);收集心脏组织采用HE染色检测小鼠心脏病理形态,Masson染色检测心肌梗死小鼠心肌纤维化程度,免疫荧光检测白细胞分化抗原68(CD68)、淋巴管内皮受体-1(LYVE-1)的表达,WB法检测LYVE-1蛋白含量的变化,流式细胞术检测纵膈淋巴结中CD68比例。结果与假手术组小鼠相比,模型组左室LVEF、LVFS显著降低(P<0.05);与模型组比较,冠心宁注射液低剂量组LVEF显著升高,LVEDD、LVESD显著降低,(P<0.05),冠心宁注射液高剂量组LVEF、LVFS显著升高,LVEDD显著降低(P<0.05)。与模型组相比,冠心宁注射液低、高剂量组、卡托普利组心肌梗死面积均减少(P<0.05)。与模型组相比,冠心宁注射液低、高剂量组梗死边缘区CD68炎性细胞浸润水平降低(P<0.05),淋巴管相关指标LYVE-1蛋白及mRNA表达增加(P<0.05),纵膈淋巴结中CD68细胞比例增加(P<0.05)。结论冠心宁注射液可明显改善MI小鼠心功能,并能够调节梗死边缘区淋巴管限制心肌组织的炎症反应,为阐明冠心宁注射液调节心脏淋巴管生成促进心肌缺血组织损伤修复的作用机制提供理论依据。Objective To investigate the effective mechanism of Guanxinning Injection in improving lymphangiogenesis to relieve ventricular remodeling after myocardial infarction(MI)in mice.Methods Male C57BL/6 mice(n=100,aged 6~8 weeks old)were randomly divided into sham-operation group,MI model group,low-dose and high-dose Guanxinning Injection groups(low-dose group,high-dose group)and captopril group(each n=20).Except of sham-operation group,MI model was established through permanent ligation of left coronary anterior descending branch in other groups.The sham-operation group and MI model group were injected intraperitoneally with 0.1 ml of saline,the low-dose and high-dose groups were injected intraperitoneally with 2.5 ml/kg and 5 ml/kg of Guanxinning Injection,respectively,and captopril group was given orally 23.4 ml/kg of captopril once a day for 28 d.After treatment for 4 weeks,the levels of left ventricular ejection fraction(LVEF),left ventricular fraction shortening(LVFS),left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)were detected by using echocardiogram.The samples of cardiac tissue were collected for detecting cardiac pathological morphology after HE staining,and severity of myocardial fibrosis was detected after Masson staining.Expressions of leukocyte differentiation antigen 68(CD68)and lymphatic vascular endothelial receptor-1(LYVE-1)were detected by using immunofluorescence.The changes of LYVE-1 protein content were detected by using Western blotting assay,and CD68 proportion in mediastinal lymph nodes was detected by using flow cytometry.Results LVEF and LVFS decreased significantly in MI model group compared with sham-operation group(P<0.05).Compared with IM model group,LVEF increased significantly,and LVEDD and LVESD decreased significantly(P<0.05)in low-dose group,LVEF and LVFS increased significantly,and LVEDD decreased significantly(P<0.05)in high-dose group.Compared with IM model group,MI area decreased in low-dose group,high-dose group and captopril gro

关 键 词：心肌梗死 冠心宁注射液 淋巴管新生 炎症反应 小鼠 

分 类 号：R542.22[医药卫生—心血管疾病]