艾司西酞普兰对慢性心力衰竭大鼠心肌纤维化的影响及其与5-羟色胺、转化生长因子-β1的关系  

The effect of escitalopram on myocardial fibrosis in rats with chronic heart failure and its relationship with 5-hydroxytryptamine and,transforming growth factor β1

作　　者：史钰芳 康永安 谭知零[1] 苗思露 马玉琴 王庆海 Shi Yufang;Kang Yong'an;Tan Zhiling;Miao Silu;Ma Yuqing;Wang Qinhai(Department of Cardiology,Yichang Second People's Hospital,Yichang 443000,Hubei,China)

机构地区：[1]宜昌市第二人民医院/三峡大学附属第二人民医院心血管内科,湖北宜昌443000

出　　处：《中国医学前沿杂志(电子版)》2025年第2期40-47,共8页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

基　　金：湖北省卫生健康委科研项目(WJ2023M155)。

摘　　要：目的 探讨艾司西酞普兰(escitalopram,ESC)对慢性心力衰竭大鼠心肌纤维化的作用,并观察其对5-羟色胺(5-hydroxytryptamine,5-HT)、5-羟色胺2B受体[5-hydroxytryptamine receptor 2B,5-HT (2B)受体]、转化生长因子-β1(transforming growth factor β1,TGF-β1)、Smad同源物3 (recombinant SMAD family member 3,Smad3)等分子的影响。方法 42只SPF级雄性SD大鼠采用分层随机化法分为假手术组、模型组、低剂量ESC组(ESC-L组)、常规剂量ESC组(ESC-M组)、高剂量ESC组(ESC-H组)、ESC+卡麦角林组(ESC+Cabaser组)、卡麦角林组(Cabaser组)。除假手术组外,其他6组均采用腹主动脉缩窄术构建大鼠慢性心力衰竭模型,通过血浆N-末端B型利钠肽原(N-terminal pro-B-type natriuretic peptide,NTpro-BNP)差异检测模型构建是否成功。以上各组予以相应药物干预后,留取血浆、心肌组织,通过Masson染色检测大鼠心肌纤维化水平,ELISA检测血浆5-HT、TGF-β1水平,Western blotting检测大鼠心肌5-HT (2B)受体及Samd3表达量。此外,通过基因表达综合数据库(Gene Expression Omnibus,GEO)下载转录组测序数据,分析各心力衰竭组与假手术组心肌组织5-HT (2B)受体与TGF-β1表达量变化以及相关性。结果 比较各组心肌纤维化面积,ESC-L组、ESC-M组以及ESC-H组均低于模型组(P<0.001),ESC+Cabaser组与模型组之间无明显差异。模型组血浆5-HT水平高于ESC-L组、ESC-M组以及ESC-H组(P<0.001),与ESC+Cabaser组差异无统计学意义(P>0.05)。ESC-L组、ESC-M组、ESC-H组以及ESC+Cabaser组5-HT (2B)受体表达水平均低于模型组(P<0.05)。ESC-L组、ESC-M组以及ESC-H组TGF-β1水平均低于模型组(P<0.05),而ESC+Cabaser组与模型组TGF-β1水平差异无统计学意义(P>0.05)。GEO数据集分析显示,心力衰竭组心肌组织中5-HT (2B)受体(P<0.01)与TGF-β1(P<0.001)转录水平高于假手术组。5-HT (2B)受体与TGF-β1之间存在较强的正相关(r=0.72,P<0.001)。结论 ESC能够通过降低外周血5-HTObjective To investigate the effect of escitalopram(ESC)on myocardial fibrosis in chronic heart failure rats,and to observe its impact on molecules such as 5-hydroxytryptamine(5-HT),5-hydroxytryptamine receptor 2B[5-HT(2B)receptor],transforming growth factorβ1(TGF-β1),and recombinant SMAD family member 3(Smad3).Methods A total of 42 male Sprague-Dawley(SD)rats of SPF grade were stratified and randomly assigned into sham operation group(Sham),model group(Model),low-dose ESC group(ESC-L),conventional dose ESC group(ESC-M),high-dose ESC group(ESC-H),ESC+Cabaser group(ESC+Cabaser),and Cabaser group(Cabaser).Except for the Sham group,the other six groups were abdominal aortic constriction to induce a chronic heart failure model in rats.The success of model construction was verified by detecting the difference in plasma N-terminal pro-B-type natriuretic peptide(NTpro-BNP)levels.After administering the corresponding drug interventions to each group,plasma and myocardial tissues were collected.The level of myocardial fibrosis in rats was detected by Masson staining,the levels of plasma 5-HT and TGF-β1 were measured by ELISA,and the expression levels of 5-HT(2B)receptor and Smad3 in rat myocardium were detected by Western blotting.In addition,sequencing data was downloaded from the Gene Expression Omnibus(GEO)database to analyze the changes and correlation of 5-HT(2B)receptor and TGF-β1 expression levels in myocardial tissue between the heart failure group and the normal group.Results The results showed that the myocardial fibrosis area was significantly lower in the ESC-L,ESC-M,and ESC-H groups than that in the Model group(P<0.001),while there was no significant difference between the ESC+Cabaser group and the Model group.The plasma 5-HT levels in the Model group were significantly higher than those in the ESC-L group,ESC-M group,and ESC-H group(P<0.001),and there was no difference compared to the ESC+Cabaser group.The expression levels of 5-HT(2B)receptors in the ESC-L group,ESC-M group,ESC-H group,and ESC+Cabaser g

关 键 词：艾司西酞普兰 慢性心力衰竭 心肌纤维化 5-羟色胺 转化生长因子β1 

分 类 号：R541.6[医药卫生—心血管疾病]