五味子乙素基于硫氧还蛋白互作蛋白/硫氧还蛋白/凋亡信号调节激酶1通路对大鼠急性心肌缺血损伤的影响  

Effect of Schisandrin B on acute myocardial ischemic injury in rats based on thioredoxin interaction protein/thioredoxin/apoptosis signal-regulating kinase 1 pathway

作　　者：王媛 刘晟楠 郝娜[1] 姜红[1] 李立萍[1] 张勤增[1] 解丽君[1] WANG Yuan;LIU Shengnan;HAO Na;JIANG Hong;LI Liping;ZHANG Qinzeng;XIE Lijun(Institute of Materia Medica,Hebei Academy of Medical Science,Hebei Province,Shijiazhuang050021,China)

机构地区：[1]河北省医学科学院药物研究所,河北石家庄050021

出　　处：《中国医药导报》2023年第10期23-27,41,共6页China Medical Herald

基　　金：河北省科技厅应用基础研究重点项目(179676127D)。

摘　　要：目的探讨五味子乙素(SchB)对急性心肌缺血损伤大鼠硫氧还蛋白互作蛋白(TXNIP)、硫氧还蛋白(TRX)与凋亡信号调节激酶1(ASK1)表达的影响。方法选取60只SPF级雄性SD大鼠(体重210~250 g),采用随机数字表法将其分为对照组、模型组及SchB低、中、高剂量组(20、40、80 mg/kg),每组12只。SchB低、中、高剂量组灌胃相应药物(10 ml/kg),对照组和模型组灌胃等量1%羧甲基纤维素钠,1次/d,连续14 d。末次给药2 h后,模型组及SchB低、中、高剂量组结扎冠状动脉左前降支建立心肌缺血模型,对照组仅开胸不结扎。缺血3 h后测量五组平均动脉压(MAP)、左心室收缩压(LVSP)、左心室舒张末压(LVEDP)、左心室内压上升或下降最大速率(±dp/dtmax)、左心室发展压(LVDP),然后处死大鼠。取五组心脏组织,采用酶标仪测定心肌组织中脂质过氧化物(LPO)、谷胱甘肽(GSH)含量和TRX还原酶(TrxR)活性;采用TTC染色测定心肌梗死面积;采用TUNEL染色观察心肌细胞凋亡情况;采用免疫印迹法检测TXNIP、TRX、胱天蛋白酶-3(caspase-3)、ASK1、p-ASK1水平。结果模型组MAP、LVDP、±dp/dtmax、GSH、TrxR、TRX表达低于对照组,LVEDP、LPO、心肌细胞凋亡指数(AI)及TXNIP、caspase-3、p-ASK1/ASK1表达高于对照组(P<0.05)。SchB低、中、高剂量组GSH、TrxR、TRX蛋白表达高于模型组,LPO、心肌梗死面积低于模型组(P<0.05)。SchB中、高剂量组MAP、LVDP、±dp/dtmax高于模型组,LVEDP、心肌细胞AI及TXNIP、caspase-3、p-ASK1/ASK1表达低于模型组(P<0.05)。SchB高剂量组MAP、LVDP、±dp/dtmax、TRX表达高于SchB低剂量组,LVEDP、心肌梗死面积、心肌细胞AI及TXNIP、caspase-3、p-ASK1/ASK1表达低于SchB低剂量组(P<0.05)。结论SchB可能通过TXNIP/TRX/ASK1通路减轻氧化应激损伤,抑制心肌细胞凋亡而发挥心肌保护作用。Objective To study the effect of Schisandrin B(Sch B)on the expression of thioredoxin interaction protein(TXNIP),thioredoxin(TRX),and apoptosis signal-regulating kinase 1(ASK1)in acute myocardial ischemic injury of rats.Methods Sixty SPF male SD rats(body weight 210-250 g)were selected and divided into control group,model group,and SchB low-dose,medium-dose,and high-dose groups(20,40,80 mg/kg)by random number table method,with 12 rats in each group.SchB low-dose,medium-dose,and high-dose groups were intragastrically given the corresponding drug(10 ml/kg),while control group and model group were intragastrically given 1%sodium carboxymethylcellulose,once a day,for consecutive 14 days.Two hours after the last administration,myocardial ischemia model was establishedby ligation of the left anterior descending branch of coronary artery in the model group and SchB low-dose,medium-dose,high-dose groups,while the control group only underwent thoracotomy without ligation.Mean arterial pressure(MAP),left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),maximum rate of rise or fall of left ventricular pressure(±dp/dtmax),and left ventricular developmental pressure(LVDP)were measured at 3 h of ischemia.Then the rats were killed and the heart tissue was taken.The contents of lipid peroxides(LPO),glutathione(GSH),and the activities of TRX reductase(TrxR)of heart tissues in five groups were determined by enzyme-labeled instrument.TTC staining was used to measure myocardial infarction size.Myocardial cell apoptosis was observed by TUNEL staining.TXNIP,TRX,cysteine aspartic acid specific protease-3(caspase-3),ASK1,and p-ASK1 levels were detected by Western blot.Results The MAP,LVDP,±dp/dtmax,expression of GSH,TrxR,and TRX in model group were lower than those in control group,while the LVEDP,LPO,myocardial apoptosis index(AI),and expressions of TXNIP,caspase-3,and p-ASK1/ASK1 in model group were higher than those in control group(P<0.05).The expression of GSH,TrxR,and TRX in SchB low-dose,medium

关 键 词：五味子乙素 急性心肌缺血 氧化应激 细胞凋亡 

分 类 号：R965[医药卫生—药理学]