山茱萸多糖对大鼠心肌缺血再灌注损伤的保护作用及机制探讨  被引量:20

Protective effect and mechanism of polysaccharide from Fructus Corni in myocardial ischemia / reperfusion injury model of rats

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作  者:张晓京[1] 来丽娜[1] 张晓一[1] 宋丽华[1] 雷静文[1] 刘芳[1] 郭春花[1] 宋晓亮[1] 

机构地区:[1]长治医学院药学系

出  处:《中国临床药理学与治疗学》2016年第7期759-764,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基  金:长治医学院科技创新团队项目(CX201409);山西省高等学校"131"领军人才工程项目

摘  要:目的:观察山茱萸多糖(polysaccharide from Fructus Corni,PFC)对大鼠心肌缺血再灌注(ischemia/reperfusion,I/R)损伤的保护作用,并探讨可能机制。方法:40只雄性SD大鼠,随机分为伪手术组(Sham)、缺血再灌注组(I/R)、PFC低、中、高处理组(25、100、200 mg·kg-1·d-1)。给药14 d后,采用结扎左冠状动脉前降支35 min,再灌注120 min的方法建立心肌I/R损伤模型。观察各组大鼠在缺血前、缺血30 min、复灌5、30、60、120 min时的左室收缩压(left ventricular systolic pressure,LVSP)、左室舒张末期压(left ventricular end diastolic pressure,LVEDP)和左室压上升、下降最大速率(±dp/dtmax);HE染色观察心肌组织病理改变;比色法测定血浆SOD、GSH-Px、CK活性和MDA含量;RT-PCR检测心肌肌浆网钙酶(sarcoplasmic reticulum calcium ATPase 2a,SERCA2a)mRNA的表达。结果:与I/R组相比,PFC(100、200 mg·kg-1·d-1)组LVSP和±dp/dtmax明显升高(P<0.01),LVEDP值显著降低(P<0.01);光镜下可见I/R组心肌纤维排列紊乱、断裂,水肿,炎细胞浸润;PFC(100、200mg·kg-1·d-1)组心肌细胞排列规则,仅有轻度充血、水肿。与Sham组比较,I/R组SOD、GSH-Px活性均显著降低(P<0.01),MDA和CK含量显著增高(P<0.01);与I/R组相比,PFC(100、200mg·kg-1·d-1)组SOD、GSH-Px活性增加,MDA含量降低(P<0.01),PFC(25 mg·kg-1·d-1)组与I/R组相比差异无统计学意义(P>0.05);而CK含量在PFC(25、100、200 mg·kg-1·d-1)组均显著降低(P<0.01);PFC(100、200mg·kg-1·d-1)组SERCA2a ATPase mRNA的表达较I/R组增多(P<0.01)。结论:山茱萸多糖可显著减轻大鼠心肌I/R损伤,其机制与减轻氧化应激,抑制细胞内钙超载有关。AIM: To investigate the protective effect and mechanism of polysaccharide from Fructus Corni ( PFC ) against ischemia/reperfusion (I/R) injury in rat myocardium. METHODS: 40 male SD rats were randomly divided into Sham operation group, I/R group, low-dose PFC group (25mg·kg^-1· d^-1), middle-dose PFC group ( 100mg·kg^-1· d^-1) , and high-dose PFC group ( 200 mg·kg^-1· d^-1) , ten in each group. The model of myocardial I/R injury was made by 35 rain occlusion of left anterior descending branch (LAD) of coro- nary artery followed by 120 min reperfusion. Left ventricular systolic pressure (LVSP) , left ventricular end diastolic pressure(LVEDP) and±dp/dtmax was recorded by BL-420S before ischemia, 30 rain after ischemia, 5, 30,60 min and 120 min after reperfu- sion. Stained with HE, pathological changes in myo-cardial tissue were observed with microscopy. The activities of SOD, GSH-Px, CK and content of MDA in the plasma were measured by colorimetry. The expression of sarcoplasmic reticulum calcium ATPase 2a mRNA was determined by RT-PCR. RESULTS: Compared with I/R group, LVSP, ± dp/dtmax were increased significantly ( P 〈 0.01 ), LVEDP were decreased(P 〈 0.01) in PFC group (100,200 mg·kg^-1· d^-1). Under microscope, serious cardiac ceils disorders, fracture, mild to moderate hypere- mia and edema and inflammatory cell infiltration were observed in the I/R group. However, in the high-dose PFC group and mid-dose PFC group, my- ocardial cells disorders and destruction decreased significantly, and some organizations were still mild hyperemia and edema. The activities of SOD, GSH- Px in the high-dose PFC group and mid-dose PFC group were obviously increased and the content of MDA was reduced in comparison with that of the I/R group. At the same time, the content of CK in the high-dose PFC group, mid-dose PFC group and low- dose PFC group were reduced in comparison with that of the I/R group. Compared with I/R group, the expressions of SERCA2a mRNA were incre

关 键 词:山茱萸 多糖 大鼠 缺血/再灌注 心功能 

分 类 号:R965.2[医药卫生—药理学]

 

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