磷酸肌酸对大鼠血液流变学的影响及其作用机制  

Effect of phosphocreatine on hemorheology in rats and its possible mechanism

作　　者：吕莉[1] 韩国柱[1] 孟璇[1] 邹玲莉[2] 任闯[1] 高璇[1] 王真子[1] 

机构地区：[1]大连医科大学药学院,大连116044 [2]大连市第三人民医院,大连116033

出　　处：《中国新药杂志》2013年第16期1936-1941,共6页Chinese Journal of New Drugs

摘　　要：目的:研究磷酸肌酸(PCr)对大鼠血液流变学的影响及其可能机制,为其心肌保护等作用的临床应用提供实验依据。方法:大鼠静脉注射低、高剂量(0.5,1.0 g.kg-1)PCr后不同时间取血,测定有关血液流变学参数,并分别与生理盐水对照组比较,计算各参数的抑制率(I%),以此作为效应强度(E)指标;根据效应-时间曲线计算峰效应Emax、效应达峰时间tmax,E和作用持续时间td。离子对反相HPLC法测定红细胞(RBC)中外源性PCr及其代谢物肌酸(Cr)和相关三磷酸腺苷(ATP)。结果:低、高剂量PCr明显降低低/高切变率全血黏度(Emax为30.48%～40.23%/18.97%～29.34%)、血小板聚集率(Emax为54.45%～62.50%)和RBC溶血率(Emax为49.23%～71.95%),对血浆黏度也有一定降低作用(Emax为17.83%～23.55%)(P<0.01);tmax,E分别为20和10 min,td为240或120 min。给药后RBC中未测出外源性PCr,但检出其代谢产物Cr和相关ATP,并持续较长时间(>300 min),其Cmax分别为36～68和143～252μg.mL-1,tmax分别为120和60～90 min。结论:PCr可明显改善大鼠血液流变学,其机制可能与PCr诱发的RBC中ATP和Cr水平升高有关。Objective： To determine the effect of phosphocreatine （PCr） on hemorrheology in rats and its possible mechanism for providing experimental evidence for its clinical use in myocardial protection. Methods： Af- ter iv administrations, blood samples were taken from rats at various time points for measuring related hemorheologi- cal parameters. As compared with control, percent inhibition of each parameter in PCr-treated rats was calculated and served as effect potency （E） index. According to E-T curve, peak effect （Emax） , the time to reach peak effect （t E） and duration of effect （td） were calculated. An ion-pair reversed-phase HPLC assay was used to deter- mine PCr and its metabolite creatine （Cr） as well as ATP in red blood ceils （RBC）. Results： PCr at doses of O. 5 and 1.0 g kg-1 significantly reduced whole blood viscosity at low and high shear rates （ E was 30.48% - 40.23% and 18.97% - 29.34% , respectively） , platelet aggregation rates （E was 54.5% - 62.5% ） , and RBC hemolysis rates （E was 49.23% -71.95% ） with t E 20 or 10 min and td 240 or 120 rain. The plasma viscosity was also reduced to some extent in PCr-treated rats. No exogenous PCr could be detected in RBC of PCr- treated rats. By contrast, PCr-derived Cr and related ATP were detected in significant amount and lasted for rela- tively longer time （ 〉 300 rain） with t 120 and 60 -90 min, respectively. Conclusion： PCr can markedly im- prove hemorheology of rats ; the action mechanism is related to increased ATP and Cr levels in RBC induced by PCr.

关 键 词：磷酸肌酸 肌酸 三磷酸腺苷 血液流变学 高效液相色谱 大鼠 

分 类 号：R961[医药卫生—药理学]