基于mTOR-p70S6K/4EBP1信号通路探讨淫羊藿苷抑制病毒性心肌炎模型小鼠心肌损伤的实验研究  

Effects of tcariin on mTOR-p70S6K/4EBP1 Siiggnnaalliinngg PPaatthhwwaayy iinn Mice with Viral Myocarditis

作　　者：黄莉芳 刘超权 HUANG Lifang;LIU Chaoquan(Hainan West Central Hospital,Danzhou 57i700,Hainan,China)

机构地区：[1]海南西部中心医院,海南詹州571700

出　　处：《辽宁中医药大学学报》2023年第9期52-56,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：海南省自然科学基金面上项目(814342);海南省医药卫生科研项目(15A200081)。

摘　　要：目的探讨淫羊藿苷对病毒性心肌炎小鼠雷帕霉素靶蛋白(mTOR)-p70核糖体蛋白S6激酶(p70S6K)/真核细胞起始因子4E结合蛋白1(4EBP1)信号通路的影响。方法健康雄性BALB/c小鼠65只,分为对照组(n=11)和模型组(n=54)。模型组采用柯萨奇病毒B3标准株腹腔接种建立病毒性心肌炎小鼠模型,对照组给予等体积不含病毒的培养液腹腔注射。将造模成功的小鼠随机分为模型组(n=11)、淫羊藿苷低浓度组(n=12)、淫羊藿苷高浓度组(n=12)和卡托普利组(n=11)。模型组与对照组分别予以0.5%羧甲基纤维素钠;淫羊藿苷低、高浓度组分别予以8、16 mg/mL淫羊藿苷混悬液;卡托普利组予以10 mg/mL卡托普利混悬液;各组药物灌胃剂量均为10 mL/kg,每日1次,连续干预60 d。检测比较各组小鼠心脏超声指标,心肌组织病理评分,心肌胶原容积分数(CVF),血清Ⅰ型前胶原羧基端肽(PⅠCP)、Ⅲ型前胶原氨基端原肽(PⅢNP)、转化生长因子β1(TGF-β1)含量,以及心肌组织磷酸化mTOR(p-mTOR)、磷酸化p70S6K(p-p70S6K)、磷酸化4EBP1(p-4EBP1)表达水平。结果干预后,与模型组比较,各组小鼠左室收缩末期内径(LVEDs)、左室舒张末期内径(LVEDd)较低,左室内径缩短率(FS)水平较高,心肌组织病理学评分较低,心肌CVF较低,血清PⅠCP、PⅢNP、TGF-β1含量较低,心肌组织p-mTOR、p-p70S6K、p-4EBP1表达水平较低,差异有统计学意义(P<0.05),且淫羊藿苷干预组呈一定量效关系。结论淫羊藿苷能剂量依赖性地改善病毒性心肌炎小鼠心脏收缩舒张功能,减轻心肌组织病理损伤,延缓心肌纤维化,其作用可能与抑制mTOR-p70S6K/4EBP1信号通路活性有关。Objective To analysis the effect of icarin on rapamycin target protein(mTOR)-p70 ribosomal protein S6 kinase(p70S6K)/eukaryotic initiation factor 4E binding protein 1(4EBP1)signaling pathway in mice with viral myocarditis.Methods 65 healthy male BALB/c mice were divided into control group(n=11)and model building group(n=54).The viral myocarditis mice model was established by intraperitoneal inoculation of coxsackievirus B3 standard strain,and the control group was given the same volume of culture solution without virus by intraperitoneal injection.The mice successfully established the models were randomly divided into model group(n=11),icarin low-concentration group(n=12),icarin high-concentration group(n=12)and captopril group(n=11).The modei group and the control group were respectively given 0.5%carboxymethylcellulose sodium;mice in the icarin low-concentration,high-concentration group were respectively given 8 mg/mL,16 mg/mL icarin suspension;the captopril group was given 10 mg/mL captopril suspension;the intragastric dose of each group was 10 mL/kg,once a day,continuous administration for 60 d.The cardiac ultrasound indexes,myocardial histopathological score,myocardial collagen volume fraction(CVF),serum procollagen type I carboxy terminal peptide(P I CP),procollagen type III amino terminal peptide(P II NP)and transforming growth factor-β1(TCF-β1)contents,the expression levels of phosphorylated mTOR(p-mTOR),phosphorylated P70S6K(p-p7OS6K)and phosphorylated 4EBPI(p-4EBPI)in myocardium were detected and compared in each group.Results After treatment,compared with model group,the left ventricular end systolic diameter(LVEDs)and left ventricular end diastolic diameter(LVEDd)were lower,the left ventricular diameter shortening rate(Fs)levels were higher,the myocardial histopathological scores were lower,the myocardial CVF were lower,and the serum contents of P I CP,P II NP and TGF-β1 were lower,the expression levels of P-mTOR,p-p7OS6K and p-4EBP1 in myocardium were lower in mice of each group,the differences we

关 键 词：淫羊藿苷 病毒性心肌炎 心肌纤维化 雷帕霉素靶蛋白 p70核糖体蛋白S6激酶 真核细胞起始因子4E结合蛋白1 

分 类 号：R282[医药卫生—中药学] R542.21[医药卫生—中医学]