基于miR-155/BDNF/TrkB轴探讨西红花酸对急性心力衰竭大鼠心功能及心室重构的影响  

Effects of Crocin on Cardiac Function and Ventricular Remodeling in Rats with Acute Heart Failure Based on miR-155/BDNF/TrkB Axis

作　　者：王琰淏 李燕[1] 张松雨[1] 周晓铎 王颖 WANG Yanhao;LI Yan;ZHANG Songyu;ZHOU Xiaoduo;WANG Ying(Nanyang Central Hospital,Nanyang 473000,Henan,China)

机构地区：[1]南阳市中心医院,河南南阳473000 [2]郑州大学第一附属医院

出　　处：《中西医结合心脑血管病杂志》2023年第20期3730-3734,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：2019年河南省医学科技攻关计划联合共建项目(No.LHGJ20190296)。

摘　　要：目的:观察西红花酸对急性心力衰竭大鼠心功能及心室重构的影响,并探讨可能的机制。方法:取45只SD大鼠,随机选取10只设置为Sham组;其余大鼠建立急性心力衰竭模型,随机分为急性心力衰竭组、Crocetin组、Crocetin联合转染组,剔除建模失败及后续实验死亡的大鼠后,每组均纳入10只。Crocetin联合转染组左心腔内注射100μL微小RNA(miR)-155激活剂腺病毒(5×10^(12)μg/mL)后腹腔注射西红花酸100 mg/kg,Crocetin组腹腔注射西红花酸100 mg/kg,Sham组、急性心力衰竭组腹腔注射等量二甲基亚砜(DSMO),每日1次,持续2周。检测心功能指标及心室重构指标;逆转录实时荧光定量聚合酶链式反应(qRT-PCR)检测心肌组织miR-155表达量;双荧光素酶实验验证miR-155与BDNF的靶向关系;蛋白免疫印迹法(Western Blot)检测心肌组织脑源性神经营养因子(BDNF)、酪氨酸激酶受体B(TrkB)、磷酸化-TrkB(p-TrkB)蛋白表达。结果:与Sham组比较,急性心力衰竭组左室射血分数(LVEF)、左室短轴缩短率(LVFS)降低,左室后壁厚度(LVPW)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)增加(P<0.05);与急性心力衰竭组比较,Crocetin组LVEF、LVFS升高,LVPW、LVEDD、LVESD降低(P<0.05);与Crocetin组比较,Crocetin联合转染组LVEF、LVFS降低,LVPW、LVEDD、LVESD增加(P<0.05)。与Sham组比较,急性心力衰竭组miR-155表达量升高(P<0.05);与急性心力衰竭组比较,Crocetin组miR-155表达量降低(P<0.05);与Crocetin组比较,Crocetin联合转染组miR-155表达量升高(P<0.05)。双荧光素酶结果显示,BDNF是miR-155的一个靶基因,两者结合位点是BDNF的3′-UTR片段。与Sham组比较,急性心力衰竭组BDNF蛋白表达、p-TrkB/TrkB降低(P<0.05);与急性心力衰竭组比较,Crocetin组BDNF蛋白表达、p-TrkB/TrkB升高(P<0.05);与Crocetin组比较,Crocetin联合转染组BDNF蛋白表达、p-TrkB/TrkB降低(P<0.05)。结论:西红花酸可抑制急性心力衰竭大鼠心室重构,Objective:To observe the effects of crocetin on cardiac function and ventricular remodeling in rats with acute heart failure and explore the possible mechanism.Methods:A total of 45 SD rats were selected and 10 rats were randomly selected as Sham group.The remaining rats were selected to construct acute heart failure model and randomly divided into acute heart failure group,Crocetin group and Crocetin co-transfection group.The rats that failed modeling,and subsequent experimental deaths were excluded,with 10 rats in each group.The Crocetin co-transfection group was intraperitoneally injected with 100μL micRNAs(miR)-155 activator adenovirus(5×10^(12)μg/mL)in the left ventricular cavity once a day for 2 weeks.Crocetin group was intraperitoneally injected with 100 mg/kg crocetin once a day for 2 weeks.The Sham group and acute heart failure group were injected with dimethyl sulfoxide(DSMO)once a day for 2 weeks.Cardiac function index and ventricular remodeling index were detected in each group.The expression of miR-155 in myocardium was detected by quantitative reverse transcription polymerase chain reaction(qRT-PCR).Dual luciferase assay was used to verify the targeting relationship between miR-155 and brain-derived neurotrophic factor(BDNF).The protein expressions of BDNF,tyrosine kinase receptor B(TrkB),and phosphorylated TrkB(p-TrkB)detected by Western Blot.Results:Compared with the Sham group,left ventricular ejection fraction(LVEF)and left ventricular short axis shortening rate(LVFS)decreased in acute heart failure group,and left ventricular posterior wall thickness(LVPW),left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)increased(P<0.05).Compared with the acute heart failure group,LVEF and LVFS in the Crocetin group increased,while LVPW,LVEDD and LVESD decreased(P<0.05).Compared with Crocetin group,LVEF and LVFS in Crocetin co-transfection group decreased,while LVPW,LVEDD and LVESD increased(P<0.05).Compared with the Sham group,the expression of miR-155 in the ac

关 键 词：急性心力衰竭 西红花酸 心功能 心室重构 大鼠 实验研究 

分 类 号：R285.5[医药卫生—中药学]