红花黄色素对心肌梗死后的心室重构及MAPK/mTOR信号通路的影响  

Effects of Safflower Yellow on Ventricular Remodeling and MAPK/mTOR Signaling Pathway after Myocardial Infarction

作　　者：许星明 周芳丽[2] 孙敏燕 骆欣怡 徐晨曦 万昆 王晓敏[1] XU Xingming;ZHOU Fangli;SUN Minyan;LUO Xinyi;XU Chenxi;WAN Kun;WANG Xiaomin(Jiangxi University of Chinese Medicine,Nanchang 330004;Nanchang Hongdu Hospital of TCM,Nanchang 330004)

机构地区：[1]江西中医药大学,南昌330004 [2]南昌市洪都中医院,南昌330006

出　　处：《中药药理与临床》2023年第6期58-63,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：江西省教育厅科学技术研究项目(编号:GJJ190625);江西省卫生健康委科技项目(编号:202211677);江西中医药大学中西医结合一级学科(江西省双一流学科,编号:zxyylxk20220103);江西省高水平本科教学团队项目。

摘　　要：目的:研究红花黄色素对心肌梗死后的心室重构及丝裂原活化蛋白激酶(MAPK)/雷帕霉素靶蛋白(mTOR)信号通路的影响。方法:结扎左冠状动脉前降支建立心肌梗死模型,假手术对照组开胸未结扎左冠状动脉前降支。建模成功大鼠随机分为模型对照组、红花黄色素5、10 mg/kg组、依那普利1 mg/kg组,各组灌胃相应药物或腹腔注射,1次/d,连续给药4 w。Ⅱ导联心电图观察心肌电生理的变化,心脏超声测定大鼠心功能;ELISA法检测血清超敏心肌肌钙蛋白I(hs-cTn-I)和N端B型利钠肽(NT-proBNP)的含量;ELISA法检测大鼠心肌组织肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)的含量;HE染色观察心肌组织形态变化;Masson染色观察心肌梗死和心肌纤维化情况,使用Image J软件测定心脏纤维化程度;超声心动图评估心功能和容积;Western blot法检测心肌组织转化生长因子β1(TGF-β1)、P38MAPK、p-P38MAPK、mTOR、p-mTOR蛋白表达。结果:与假手术对照组比较,模型对照组大鼠Ⅱ导联ST段回落减少、心功能下降和心肌梗死面积增加、胶原沉积率升高(P<0.05),心肌组织的TNF-α含量升高、IL-10含量降低(P<0.05或P<0.01),TGF-β1蛋白表达明显上调(P<0.05),p-mTOR/mTOR比值显著降低(P<0.01);与模型对照组比较,各给药组大鼠Ⅱ导联心电图呈弓背抬高,ST段回落且下降幅度明显;心肌TNF-α含量降低、IL-10含量升高(P<0.01),心肌梗死面积减少、纤维组织沉积和中性粒细胞浸润减少,心肌组织TGF-β1蛋白表达明显下调(P<0.05),p-P38MAPK/P38MAPK、p-mTOR/mTOR比值明显升高(P<0.05);红花黄色素10 mg/kg组和依那普利1 mg/kg组血清hs-cTn-I和NT-proBNP含量明显降低(P<0.05),左心室收缩期内径(LVDs)和左心室舒张期内径(LVDd)明显降低,左心室射血分数(LVEF)和左心室缩短分数(LVFS)明显升高(P<0.05)。结论:红花黄色素能够增强心肌梗死后大鼠的心功能,减轻炎症反应,减轻心肌纤维化,抑制Objective:To investigate the effects of safflower yellow on ventricular remodeling and the mitogen-activated protein kinase(MAPK)/mammalian target of rapamycin(mTOR)signaling pathway after myocardial infarction.Methods:The model of myocardial infarction was established in rats by ligation of the left anterior descending coronary artery,while the sham operation group underwent thoracotomy without ligation of the left anterior descending coronary artery.Model rats were randomly divided into a model control group,two safflower yellow groups(5 and 10 mg/kg),and an enalapril group(1 mg/kg).The corresponding drugs were administered by gavage or intraperitoneal injection once daily for four weeks.Changes in myocardial electrophysiology were observed using lead II electrocardiography,and cardiac function was assessed by echocardiography.The levels of serum high-sensitivity cardiac troponin I(hs-cTn-I)and N-terminal pro-B-type natriuretic peptide(NT-proBNP)were determined by enzyme-linked immunosorbent assay(ELISA).The levels of tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in myocardial tissues were detected by ELISA.Myocardial tissue morphology was observed by hematoxylin-eosin staining,and myocardial infarction and fibrosis were assessed by Masson's staining.The degree of cardiac fibrosis was measured using Image J software.Cardiac function and volume were evaluated using Vevo 2100 echocardiography.The protein expression of transforming growth factorβ1(TGFβ1),p38MAPK,p-p38MAPK,mTOR,and p-mTOR in myocardial tissues was detected by Western blot.Results:Compared to the sham operation group,the model control group showed increased mortality rate and shortened survival time(P<0.05),decreased lead II ST-segment depression,declining cardiac function,increased myocardial infarction area,increased collagen deposition rate(P<0.05),increased TNF-αlevel in myocardial tissues,decreased IL-10 level(P<0.05 or P<0.01),upregulated TGFβ1 protein expression(P<0.05),and reduced p-mTOR/mTOR ratio(P<0.01).Compared with the mo

关 键 词：红花黄色素 心室重构 心肌梗死 丝裂原激活蛋白激酶/雷帕霉素靶蛋白信号通路 

分 类 号：R285[医药卫生—中药学]