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[摘要]
目的观察槲寄生黄酮苷对心肌缺血大鼠的保护作用,并进一步明确其对血小板激活因子(PAF)的调控作用。方法结扎大鼠冠状动脉左前降支造成急性心肌梗死模型,通过观察不同剂量槲寄生黄酮苷(15、75mg/kg)及PAF受体特异性阻断剂BN52021(10mg/kg)对梗死范围的影响,对比评价槲寄生黄酮苷对缺血心肌的保护作用;分离正常大鼠心肌细胞,Fluo-3/AM荧光染色,采用共聚焦显微镜技术研究,预先给予不同剂量槲寄生黄酮苷30min后对PAF(1×10-11mol/L)诱导心肌细胞钙超载的拮抗作用。结果与模型组比较,槲寄生黄酮苷和BN52021均可缩小大鼠梗死心肌范围,降低心肌梗死大鼠血清乳酸脱氢酶(LDH),丙二醛(MDA)水平,提高血清超氧化物歧化酶(SOD)水平,并成剂量效应关系。PAF可直接诱导心肌细胞钙超载,而槲寄生黄酮苷和BN52021可直接对抗这种钙超载作用。结论槲寄生黄酮苷对心肌缺血具有保护作用,作用机制与其抑制PAF诱导心肌细胞内钙超载有关,PAF信号通路阻断药物可能成为抗心肌缺血药物的研究靶点。
[Key word]
[Abstract]
Objective To investigate the protective effects of Viscum coloratum flavonoid glycosides(VCFG)against ischemic myocardial injuries in vivo of rats and to further investigate its regulatory effect on platelet activating factor(PAF).Methods The model of acute myocardial infarction rats was constructed by ligating left descending anterior branch of coronary artery.The change of myocardial infarct size(MIS)was determined to evaluate the protective effect of PAFBN 52021(10 mg/kg)and different doses of VCFG(15 and 75 mg/kg)on the myocardial ischemia of rats.Myocytes were isolated and fluorescent changes of the Fluo-3/AM-loaded cells were detected after 30 min of administration of different doses VCFG.The fluorescent intensities both before(FI0)and after(FI)the drug administration were recorded by a laser scanning confocal microscope to observe the blocking effect of VCFG on PAF-induced Ca2+ overload.Results Compared with control group,MIS was reduced by VCFG and BN 52021 and changed level of LDH,MDA,and activity of SOD in infarcted rats was recovered by VCFG or BN 52021.PAF(1×10-11 mol/L)significantly increased the intracellular free Ca2+ concentration([Ca2+]i).VCFG and BN 52021 had the inhibitory effect on PAF-induced Ca2+ overload in a dose-dependent manner.ConclusionVCFG has protective effects on myocardial ischemia of rats and the protective effects are likely mediated by the blocking of PAF-induced Ca2+ overload in cardiac myocytes.PAF Blockers may be candidate drugs for preventing cardiac injuries during ischemia/reperfusion of rats.
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[基金项目]
黑龙江省自然科学基金重点项目(ZJY0501);中国博士后基金资助项目(20070410915);黑龙江省青年科学基金资助项目(QC06C070)