藁本内酯调控PKD1/HIF-1α/VEGF通路对心力衰竭大鼠的改善作用  

Improvement effect of ligustilide on rats with heart failure by regulating PKD1/HIF-1α/VEGF pathway

作　　者：张岚 武永新 张涛 王东伟 ZHANG Lan;WU Yongxin;ZHANG Tao;WANG Dongwei(Department of Cardiology,Affiliated Zhengzhou Central Hospital,Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]郑州大学附属郑州中心医院心血管内科,河南郑州450001

出　　处：《吉林大学学报（医学版）》2024年第1期42-49,共8页Journal of Jilin University：Medicine Edition

基　　金：河南省卫健委医学科技攻关计划项目(2018010047)。

摘　　要：目的:探讨藁本内酯对心力衰竭大鼠心功能和血管生成的影响,并分析其对蛋白激酶D1(PKD1)/缺氧诱导因子1α(HIF-1α)/血管内皮生长因子(VEGF)通路的调节作用。方法:SD大鼠随机分为假手术组、模型组、藁本内酯组、PKD1/HIF-1α/VEGF信号通路阻断剂CID755673(CID)组和藁本内酯+CID组,采用冠状动脉左前降支结扎法建立心力衰竭大鼠模型,藁本内酯组大鼠尾静脉注射藁本内酯20 mg·kg^(-1),CID组大鼠腹腔注射CID 50 mg·kg^(-1),藁本内酯+CID组大鼠腹腔注射CID 50 mg·kg^(-1)后尾静脉注射藁本内酯20 mg·kg^(-1),每日1次,连续4周。采用心脏超声检查各组大鼠心功能指标,2,3,5-氯化三苯基四氮唑(TTC)染色法检测各组大鼠心肌梗死面积百分率,HE染色观察各组大鼠心肌组织病理形态表现,实时荧光定量PCR法(RT-qPCR)法和蛋白印迹法检测各组大鼠缺血区心肌组织中PKD1、HIF-1α、CD31和VEGFmRNA及蛋白表达水平。结果:与假手术组比较,模型组和CID组大鼠心肌细胞形态发生改变,细胞间隙增宽,排列紊乱,可见肌纤维断裂和炎性细胞浸润;藁本内酯组和藁本内酯+CID组大鼠心肌纤维排列相对整齐,心肌纤维断裂相对较少,炎性细胞数减少。与假手术组比较,模型组大鼠左心室射血分数(LVEF)和左心室短轴缩短率(LVFS)降低(P<0.05),左心室收缩末期内径(LVESD)和左心室舒张末期内径(LVEDD)增大(P<0.05),心肌组织中PKD1、HIF-1α、CD31和VEGF mRNA及蛋白表达水平降低(P<0.05);与模型组比较,藁本内酯组大鼠LVEF和LVFS升高(P<0.05),LVESD和LVEDD减小(P<0.05),心肌梗死面积百分率降低(P<0.05),心肌组织中PKD1、HIF-1α、CD31和VEGF mRNA及蛋白表达水平升高(P<0.05);与模型组比较,CID组大鼠LVEF和LVFS降低(P<0.05),LVESD和LVEDD增大(P<0.05),心肌梗死面积百分率升高(P<0.05),心肌组织中PKD1、HIF-1α、CD31和VEGF mRNA及蛋白表达水平降低(P<0.05);与藁本内酯组比较,藁本内酯+CID组�Objective:To discuss the effect of ligustilide on the cardiac function and angiogenesis in the rats with heart failure,and to clarify its regulatory effect on protein kinase D1(PKD1)/hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)pathway.Methods:The SD rats were randomly divided into sham operation group,model group,ligustilide group,PKD1/HIF-1α/VEGF signaling pathway inhibitor CID755673(CID)group,and ligustilide+CID group.The heart failure rat model was established by ligation of the left anterior descending coronary artery.The rats in ligustilide group were injected intravenously with 20 mg·kg^(-1) ligustilide,the rats in CID group were injected intraperitoneally with 50 mg·kg^(-1) CID,and the rats in ligustilide+CID group were injected intraperitoneally with 50 mg·kg^(-1) CID followed by intravenous injection of 20 mg·kg^(-1) ligustilide,once per day for 4 consecutive weeks.The cardiac function indexes of the rats in various groups were detected by echocardiography;the percentages of myocardial infarction areas of the rats in various groups were detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining;the pathomorphology of myocardium tissue of the rats in various groups was observed by HE staining;the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in ischemic area of myocardium tissue of the rats in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.Results:Compared with sham operation group,the rats in model group and CID group had altered myocardial cell morphology,increased intercellular gaps,disorganized arrangement,visible muscle fiber breaks and inflammatory cell infiltration;the rats in ligustilide group and ligustilide+CID group had relatively orderly myocardial fiber arrangement,fewer myocardial fiber breaks and decreased number of inflammatory cells.Compared with sham operation group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)of the rat

关 键 词：心力衰竭 血管再生 藁本内酯 蛋白激酶D1 缺氧诱导因子1Α 血管内皮生长因子 

分 类 号：R285.5[医药卫生—中药学] R541.6[医药卫生—中医学]