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作 者:郭新红[1] 曹文疆[2] 樊鑫梅[1] 邢建国 袁勇 王新春[1,2]
机构地区:[1]石河子大学药学院,新疆石河子832002 [2]石河子大学医学院第一附属医院,新疆石河子832008 [3]新疆维吾尔自治区药物研究所,乌鲁木齐830004
出 处:《中国实验方剂学杂志》2013年第5期168-172,共5页Chinese Journal of Experimental Traditional Medical Formulae
基 金:国家自然科学基金项目(81160525);国家重大新药创制项目(2012ZX09102201-009)
摘 要:目的:研究田蓟苷对大鼠心肌缺血再灌注损伤(MIRI)的保护作用及其机制。方法:60只雄性Wistar大鼠随机分为假手术组,模型组,阳性对照普萘洛尔组,田蓟苷高、中、低剂量组,每组10只。手术前1周,田蓟苷药物组灌胃给予不同剂量田蓟苷(5.0,2.5,1.5 mg.kg-1.d-1),普萘洛尔组按25 mg.kg-1.d-1灌胃,其余两组给予等量0.5%CMC-Na。采用结扎大鼠冠状动脉左前降支30 min后再灌注120 min建立MIRI模型。观察缺血期及再灌注期心电图ST段的变化和再灌注后心肌组织病理改变,测定血清中乳酸脱氢酶(LDH)、天冬氨酸转氨酶(AST)、肌酸激酶(CK)、肌酸磷酸激酶同工酶(CK-MB)、总超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性及丙二醛(MDA)、白介素-1(IL-1)、白介素-6(IL-6)、大鼠肿瘤坏死因子-α(TNF-α)的含量。结果:与模型组比较,田蓟苷药物组能降低缺血期和再灌注期的ST段抬高幅度;减轻心肌病理形态学损伤。显著减少血清心肌酶释放量(与模型组比较,P<0.01,P<0.05);田蓟苷高、中剂量组能使血清SOD,GSH-Px活性明显提高,MDA,IL-1,IL-6和TNF-α含量明显降低(与模型组比较,P<0.01,P<0.05)。结论:田蓟苷对大鼠MIRI有明显的保护作用,其机制可能与清除氧自由基及降低炎症因子的释放等因素有关。Objective:To study the mechanism and protective effects of tilianin on myocardial ischemia-reperfusion injury (MIRI) in rats. Method: Sixty Wistar rats were randomized into sham operation group, model group, positive control and tilianin high, medium, low dose groups (n=10). Rats in tilianin group were perfused with Tilianin (5.0, 2.5, 1.5 mg·kg-1·d-1) a week before operation, positive control group were perfused with propranolol at 25 mg·kg-1·d-1, to the sham operation group and the model group, 0.5% CMC-Na was given instead. The MIRI model was established by ligating left anterior descending coronary artery for 30 min and followed for 120 min. To observe the changes of ST segment on ECG during ischemia and reperfusion and pathological changes after reperfusion. The activity of lactate dehydrogenase (LDH), aminotransferase (AST), creatine kinas (CK), creatine kinase isozyme (CK-MB), superoxide dismutase (SOD), glutathion peroxidase (GSH-Px) and the contents of malondialdehyde (MDA), interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha (TNF-α) in serum were detected. Result: Compared with model group, the changes of ST segment elevation were attenuated by tilianin significantly during ischemia and reperfusion. Tilianin groups ameliorated the damage of myocardial pathomorphology markedly. Significantly the release of myocardium enzyme in serum decreased (P<0.01, P<0.05). Tilianin high, medium dose group can increase the activity of SOD, GSH-Px and decrease the content of MDA, IL-1, IL-6, TNF-α(P<0.01,P<0.05) in serum. Conclusion: Tilianin has a significant protective effect on MIRI in rats. The mechanism of cardioprotection may be associated with clearing oxygen free radial (OFR) and lowering release of inflammatory factors.
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