丹参多酚酸盐对小鼠糖尿病心肌梗死后的保护作用及初步机制探讨  

Protective effect and mechanism of salvianolate on myocardial infarction in mice with diabetes

作　　者：杨雪 蒲思颖 赵美娜 梁琦 耿静 郭栋 王瑛 胡朗 李妍 YANG Xue;PU Siying;ZHAO Meina;LIANG Qi;GENG Jing;GUO Dong;WANG Ying;HU Lang;LI Yan(Department of Cardiology,Tangdu Hospital,Air Force Medical University,Xi'an 710038,China;Department of Pharmacy,Xijing Hospital,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]空军军医大学唐都医院心血管内科,陕西西安710038 [2]空军军医大学西京医院药剂科,陕西西安710032

出　　处：《空军军医大学学报》2025年第2期145-152,共8页Journal of Air Force Medical University

基　　金：国家自然科学基金(82470388,82300443)。

摘　　要：目的探讨丹参多酚酸盐(SAL)对糖尿病小鼠心肌梗死(MI)后的保护作用及初步机制。方法将成年雄性C57BL/6J小鼠设为对照组;自发性2型糖尿病小鼠(db/db)分为模型组、阳性药组和SAL给药组(50、100、200 mg/kg),每组6只,结扎小鼠冠状动脉左前降支建立MI损伤模型。连续给药7 d。使用彩色多普勒超声设备对小鼠心脏功能各项指标进行评估。此外,运用HE染色技术对心肌组织的病理损伤进行检测。ELISA法测定小鼠血清中血管性血友病因子(vWF)、血小板内皮细胞黏附分子-1(PECAM-1)、内皮细胞选择素(E-selectin)、一氧化氮(NO)、活性氧(ROS)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)等指标;同时,利用qRT-PCR和Western blotting技术分析小鼠心肌组织中血管内皮生长因子(VEGF)、血管内皮细胞生长因子受体2(VEGFR2)、磷脂酰肌醇3-激酶(PI3K)和蛋白激酶B(Akt)的mRNA及其蛋白表达水平。结果模型组相较于对照组血糖和胰岛素水平更高,心肌组织病理损伤更严重,左心室射血分数、左心室短轴缩短率、NO水平降低(均P<0.01),左心室收缩末期内径、左心室舒张末期内径、vWF、PECAM-1、E-selectin、ROS、IL-1β、IL-6、TNF-α表达均升高(均P<0.01),VEGF、VEGFR2的mRNA和蛋白表达应激性升高(均P<0.01);与模型组比较,阳性药组和SAL不同剂量给药组可明显改善上述变化。结论SAL通过抑制炎症进程,恢复血管内皮损伤功能,调控VEGF/PI3K/Akt信号通路改善心脏功能,发挥糖尿病小鼠MI后的保护作用。Objective To investigate the protective effect and mechanism of salvianolate(SAL)on myocardial infarction(MI)in mice with diabetes.Methods Adult male C57BL/6J mice were set as the control group,and spontaneous type 2 diabetic mice(db/db)were divided into model group,positive drug group and SAL administration group(50,100,and 200 mg/kg),with 6 mice in each group.The left anterior descending coronary artery of the mice was ligated to establish an MI injury model.The drug was administered continuously for 7 d.Color Doppler ultrasound was used to evaluate the cardiac function indexes of mice.In addition,HE staining technology was used to detect the pathological damage of myocardial tissue.Von Willebrand factor(vWF),platelet endothelial cell adhesion molecule-1(PECAM-1),E-selectin,nitric oxide(NO),reactive oxygen species(ROS),interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and other indicators in mouse serum were determined by ELISA.The mRNA and protein expression levels of vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor 2(VEGFR2),phosphatidylinositol 3-kinase(PI3K),and protein kinase B(Akt)in mouse myocardial tissue were measured using qRT-PCR and Western blotting techniques.Results Compared with the control group,the blood glucose and insulin levels in the model group were higher,and the pathological damage of myocardial tissue was more serious,with decreased left ventricular ejection fraction,left ventricular fractional shortening,and NO levels(all P<0.01),increased left ventricular internal diameter at end-diastole,left ventricular internal diameter at end-systole,vWF,PECAM-1,E-selectin,ROS,IL-1β,IL-6 and TNF-α(all P<0.01),and increased mRNA and protein expressions of VEGF and VEGFR2 in stress(both P<0.01).Compared with the model group,the positive drug group and the SAL administration group treated with different doses could significantly improve the above changes.Conclusion SAL can inhibit the inflammatory process,restore the damaged function of

关 键 词：糖尿病并发症 丹参多酚酸盐 心肌梗死 内皮功能 小鼠 

分 类 号：R285.5[医药卫生—中药学]