中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2009年
2期
81-88
,共8页
张利萍%杨长瑛%王莹萍%关玥%徐瑛%张翼
張利萍%楊長瑛%王瑩萍%關玥%徐瑛%張翼
장리평%양장영%왕형평%관모%서영%장익
白藜芦醇苷%钾通道%线粒体通透转换孔%心肌%再灌注损伤
白藜蘆醇苷%鉀通道%線粒體通透轉換孔%心肌%再灌註損傷
백려호순감%갑통도%선립체통투전환공%심기%재관주손상
polydatin%potassium channels%mitochondrial permeability transition pore%myocardium%reperfusion injury
目的 探讨白藜芦醇苷(Poly)对大鼠缺血再灌注(I-R)心肌损伤的保护作用及其机制.方法 应用Langendorff室技术制备离体大鼠心脏I-R损伤模型.雄性SD大鼠随机分为对照组、模型组、Poly(25, 50和75 μmol·L-1)组、格列本脲(Gli)+Poly组、5-羟基癸酸(5-HD)+Poly组和苍术苷(Atr)+Poly组.对照组心脏由K-H液灌流110 min;模型组由K-H液灌流20 min后, 停灌30 min, 复灌60 min;Poly组在I-R处理前用含不同浓度Poly的K-H液灌流10 min;Gli+Poly和5-HD+Poly组在I-R前分别用含Gli (10 μmol·L-1)和5-HD(100 μmol·L-1)的K-H液灌流5 min,再加入Poly (50 μmol·L-1)灌流10 min;Atr+Poly组用含Poly(50 μmol·L-1)K-H液灌流10 min及停灌30 min后,先用含Atr(20 μmol·L-1)的K-H液灌流15 min, 然后改用K-H液灌流.分别记录各组停灌前、停灌30 min和复灌60 min内的左心室舒张末压(LVEDP)、左心室舒张压(LVDP)、左心室等容期压力最大变化速率(±dp/dtmax)和冠脉流量(CF)等心功能指标.心脏复灌60 min后,用氯化三苯基四氮唑染色法测定心肌梗死面积,透射电镜下检测心肌超微结构变化.结果 缺血前各组心功能参数无明显变化.与模型组相比,Poly可浓度依赖性地促进大鼠I-R后心功能的恢复,预防I-R损伤.复灌60 min后,Poly组大鼠心脏LVDP,±dp/dtmax和CF明显高于模型组;LVEDP则低于模型组;缺血前给予Poly(50 μmol·L-1)10 min可明显减小I-R后心肌梗死面积, 并改善心肌超微结构.Gli, 5-HD和Atr可阻断Poly对I-R心脏心功能参数和心肌梗死面积等的保护作用.结论 Poly具有明显的抗心肌I-R损伤作用,其心脏保护作用可能与其增加细胞膜和线粒体膜ATP敏感性钾通道开放和抑制线粒体通透转换孔开放有关.
目的 探討白藜蘆醇苷(Poly)對大鼠缺血再灌註(I-R)心肌損傷的保護作用及其機製.方法 應用Langendorff室技術製備離體大鼠心髒I-R損傷模型.雄性SD大鼠隨機分為對照組、模型組、Poly(25, 50和75 μmol·L-1)組、格列本脲(Gli)+Poly組、5-羥基癸痠(5-HD)+Poly組和蒼術苷(Atr)+Poly組.對照組心髒由K-H液灌流110 min;模型組由K-H液灌流20 min後, 停灌30 min, 複灌60 min;Poly組在I-R處理前用含不同濃度Poly的K-H液灌流10 min;Gli+Poly和5-HD+Poly組在I-R前分彆用含Gli (10 μmol·L-1)和5-HD(100 μmol·L-1)的K-H液灌流5 min,再加入Poly (50 μmol·L-1)灌流10 min;Atr+Poly組用含Poly(50 μmol·L-1)K-H液灌流10 min及停灌30 min後,先用含Atr(20 μmol·L-1)的K-H液灌流15 min, 然後改用K-H液灌流.分彆記錄各組停灌前、停灌30 min和複灌60 min內的左心室舒張末壓(LVEDP)、左心室舒張壓(LVDP)、左心室等容期壓力最大變化速率(±dp/dtmax)和冠脈流量(CF)等心功能指標.心髒複灌60 min後,用氯化三苯基四氮唑染色法測定心肌梗死麵積,透射電鏡下檢測心肌超微結構變化.結果 缺血前各組心功能參數無明顯變化.與模型組相比,Poly可濃度依賴性地促進大鼠I-R後心功能的恢複,預防I-R損傷.複灌60 min後,Poly組大鼠心髒LVDP,±dp/dtmax和CF明顯高于模型組;LVEDP則低于模型組;缺血前給予Poly(50 μmol·L-1)10 min可明顯減小I-R後心肌梗死麵積, 併改善心肌超微結構.Gli, 5-HD和Atr可阻斷Poly對I-R心髒心功能參數和心肌梗死麵積等的保護作用.結論 Poly具有明顯的抗心肌I-R損傷作用,其心髒保護作用可能與其增加細胞膜和線粒體膜ATP敏感性鉀通道開放和抑製線粒體通透轉換孔開放有關.
목적 탐토백려호순감(Poly)대대서결혈재관주(I-R)심기손상적보호작용급기궤제.방법 응용Langendorff실기술제비리체대서심장I-R손상모형.웅성SD대서수궤분위대조조、모형조、Poly(25, 50화75 μmol·L-1)조、격렬본뇨(Gli)+Poly조、5-간기계산(5-HD)+Poly조화창술감(Atr)+Poly조.대조조심장유K-H액관류110 min;모형조유K-H액관류20 min후, 정관30 min, 복관60 min;Poly조재I-R처리전용함불동농도Poly적K-H액관류10 min;Gli+Poly화5-HD+Poly조재I-R전분별용함Gli (10 μmol·L-1)화5-HD(100 μmol·L-1)적K-H액관류5 min,재가입Poly (50 μmol·L-1)관류10 min;Atr+Poly조용함Poly(50 μmol·L-1)K-H액관류10 min급정관30 min후,선용함Atr(20 μmol·L-1)적K-H액관류15 min, 연후개용K-H액관류.분별기록각조정관전、정관30 min화복관60 min내적좌심실서장말압(LVEDP)、좌심실서장압(LVDP)、좌심실등용기압력최대변화속솔(±dp/dtmax)화관맥류량(CF)등심공능지표.심장복관60 min후,용록화삼분기사담서염색법측정심기경사면적,투사전경하검측심기초미결구변화.결과 결혈전각조심공능삼수무명현변화.여모형조상비,Poly가농도의뢰성지촉진대서I-R후심공능적회복,예방I-R손상.복관60 min후,Poly조대서심장LVDP,±dp/dtmax화CF명현고우모형조;LVEDP칙저우모형조;결혈전급여Poly(50 μmol·L-1)10 min가명현감소I-R후심기경사면적, 병개선심기초미결구.Gli, 5-HD화Atr가조단Poly대I-R심장심공능삼수화심기경사면적등적보호작용.결론 Poly구유명현적항심기I-R손상작용,기심장보호작용가능여기증가세포막화선립체막ATP민감성갑통도개방화억제선립체통투전환공개방유관.
AIM To investigate the protective effect of polydatin on ischemia-reperfusion (I-R) injury in cardiac muscle and the possible mechanism. METHODS Langendorff technique was used to make I-R injury in rats. Male Sprague-Dawley rats were randomly divided into control, model, polydatin(25, 50 and 75 μmol·L-1), glibenclamide(Gli, 10 μmol·L-1)+polydatin(50 μmol·L-1), 5-hydroxydecanoate(5-HD, 100 μmol·L-1)+polydatin(50 μmol·L-1), and atractyloside (Atr, 20 μmol·L-1)+polydatin(50 μmol·L-1) groups. The hearts in control group were perfused with K-H solution for 110 min. Model group hearts were subjected to 30 min no-flow global ischemia followed by 60 min of reperfusion. The hearts in 3 polydatin groups were perfused with K-H solution containing different concentrations of polydatin for 10 min before I-R. The hearts in Gli+polydatin and 5-HD+polydatin groups were perfused with K-H solution containing Gli or 5-HD for 5 min firstly, then perfused with K-H solution containing both polydatin and Gli or 5-HD for 10 min before I-R. The hearts in Atr+polydatin group were perfused with K-H solution containing polydatin for 10 min before I-R and perfused with K-H solution containing Atr for 15 min after I-R. The cardiac function, including left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), the maximal rates of rise and decline of left ventricular pressure (±dp/dtmax), and coronary flow (CF), were recorded before, after 30 min no-flow global ischemia and, during 60 min reperfusion. Myocardial infarct size was assessed using 2, 3, 5-triphenyltetrazolium chloride method and myocardial ultrastructure was observed via transmission electron microscope after 60 min reperfusion. RESULTS There were no significant differences in cardiac functional parameters between control and model groups in pre-ischemia condition. Compared with model group, polydatin promoted a better recovery of cardiac function after I-R in a concentration-dependent manner. After 60 min of reperfusion, the values of LVDP, ±dp/dtmax and CF in polydatin groups were much higher, but LVEDP was lower than those in model group. Polydatin (50 μmol·L-1) also significantly reduced myocardial infarct size and relieved the I-R injury of myocardial ultrastructure. The protective effects of polydatin (50 μmol·L-1) on LVDP, LVEDP, ±dp/dtmax and CF, as well as the inhibitory effect on infarct size after I-R were abolished by Gli, 5-HD and Atr. CONCLUSION Polydatin has protective effect against I-R injury in rat hearts, which may be related with the opening of ATP-sensitive potassium channel located in both cell membrane and mitochondrial membrane, as well as inhibition of mitochondrial permeability transition pore opening.
