五味子乙素对大鼠急性心肌缺血损伤的保护作用  

Protective effects of Schisandrin B on the acute myocardial ischemia injury in rats

作　　者：王媛 刘晟楠 马姣姣 郝娜[4] 姜红[4] 李立萍[4] 张勤增[4] 解丽君[4] WANG Yuan;LIU Shengnan;MA Jiaojiao(Chengde Medical University,Hebei,Chengde 067000,China;不详)

机构地区：[1]承德医学院中药研究所,河北省承德市067000 [2]河北大学临床医学院 [3]河北医科大学第一医院 [4]河北省疾病预防控制中心

出　　处：《河北医药》2022年第21期3216-3220,共5页Hebei Medical Journal

基　　金：河北省科技厅应用基础研究重点项目(编号:179676127D)。

摘　　要：目的探讨五味子乙素(Schisandrin B,Sch B)对大鼠急性心肌缺血的影响及机制。方法60只雄性SD大鼠随机分为5组:对照组(C组),心肌缺血模型组(M组),低剂量五味子乙素组(Sch B 20 mg·kg^(-1)·d^(-1),M+L Sch B组)、中剂量五味子乙素组(Sch B 40 mg·kg^(-1)·d^(-1),M+M Sch B组)和高剂量五味子乙素组(Sch B 80 mg·kg^(-1)·d^(-1),M+H Sch B组),均连续灌胃给药2周后采用结扎大鼠冠状动脉左前降支法建立心肌缺血模型,对照组仅开胸不结扎。缺血3 h末Powerlab/8s多通道生理记录仪测定大鼠平均动脉压(MAP)、左心室收缩压(LVSP)、左心室舒张末压(LVDEP)测定5组心肌梗死面积;光镜和透射电镜观察心肌组织形态学改变;测定心肌组织中硫氧还蛋白还原酶TrxR的活性、脂质过氧化物(LPO)以及还原型谷胱甘肽(GSH)含量,测定心肌组织中胱硫醚-γ-裂解酶(CSE)活性和血清中内源性硫化氢(H 2S)含量,免疫组织化学法和Western blot法检测心肌组织中TXNIP、TrxR、cleaved-Caspase-3、NOX-4信号分子表达。结果与C组相比,M组大鼠LVEDP明显升高,而MAP、LVDP、±dp/dtmax明显降低(P<0.05);心肌梗死面积明显增加(P<0.05);心肌纤维排列紊乱,心肌细胞间及核周高度水肿,线粒体膜肿胀,嵴减少、溶解甚至消失。心肌组织中CSE活性、血清H 2S含量明显降低,TrxR活性、GSH含量明显降低,LPO含量以及TXNIP、NOX-4、Caspase-3等蛋白表达明显升高,差异均有统计学意义(P均<0.05)。与M组相比,M+M Sch B组、M+H Sch B组心功能及心肌形态学损伤改善;心肌梗死面积减少,心肌组织中CSE活性、血清H 2S含量明显升高,TrxR活性、GSH含量明显升高,LPO含量以及TXNIP、NOX-4、Caspase-3等蛋白表达明显降低(P<0.05)。结论Sch B可以通过提高内源性H 2S含量,调节机体抗氧化还原TXNIP/TRX系统,抑制TXNIP表达,促进TRX表达及活性,从而减轻大鼠急性心肌缺血损伤,保护心肌功能。Objective To investigate the protective effects of Schisandrin B(Sch B)on the acute myocardial ischemia injury in rats.Methods Sixty male SD rats were randomly divided into five groups:control group,myocardial ischemia model group(group M),low-dose schisandrin B group(SchB 20mg·kg^(-1)·d^(-1),M+L SchB group),medium-dose schisandrin B group(SchB 40mg·kg^(-1)·d^(-1),M+M SchB group)and high-dose schisandrin B group(SchB 80mg·kg^(-1)·d^(-1)),M+H SchB group).After twoweek continuous intragastric administration,the models of myocardial ischemia model were established by ligating the left anterior descending coronary artery in group M and SchB group,however,the rats in control group underwent sham operation only.At the end of 3h,the hemodynamic indexes such as mean arterial pressure(MAP),left ventricular systolic pressure(LVSP)and left ventricular end diastolic pressure(LVDEP)were measured.The myocardial infarction area of each group was measured.The morphological changes of myocardium were observed by light microscope and transmission electron microscope.The activity of thioredoxin reductase TrxR,the content of lipid peroxide(LPO)and reduced glutathione(GSH)in myocardial tissue,the activity of cystathionine-γ-lyase(CSE)and the content of endogenous hydrogen sulfide(H2S)in serum were measured.The expressions levels of TXNIP,TrxR,cleaved-Caspase-3 and NOX-4 signal molecules in myocardial tissue were detected by immunohistochemistry and Western blotting.Results Compared with those in control group,thelevels of LVEDP in group M were significantly increased,while the levels of MAP,LVDP and±dp/dtmax were significantly decreased,and the myocardial infarction area was increased significantly.Light and electron microscope observation showed that the arrangement of myocardial fibers was disordered,the myocardial cells and perikaryocytes were highly edematous,the mitochondrial membrane was swollen,and the cristae was decreased,dissolved or even disappeared.The activity of CSE,the serum levels of H 2S,the activity of TrxR,

关 键 词：五味子乙素 急性心肌缺血 硫化氢 硫氧还蛋白相互作用蛋白 硫氧还蛋白 氧化应激 

分 类 号：R542.2[医药卫生—心血管疾病]