泽兰乙醇提取物对大鼠离体心肌缺氧损伤的影响及机制

摘要

Objective To observe the effect of ethanol extract of Lycopus lucidus Turcz (ELT) on myocardial hypoxia injury (HI) of rats in vitro and to investigate the mechanism. Methods Forty male SD rats were randomly divided into the normal control (NC)group ,HI model group,ELT group,and ELT + LY294002 group with 10 rats in each. The atrial perfusion models were established in the left atria of rats in each group. Rats in the NC group were perfused with oxygen-sat-urated HEPES buffer,while in the other three groups,we established the acute myocardial HI models. Rats in the ELT group were perfused with ethanol extract of ELT (0. 1 mg mL),LY294002 group with LY294002 (1. 0 mol/ L) and ethanol extract of ELT (0. 1 mg/ mL). The atrial pulse pressure at the end of first cycle ,7th cycle,and 13th cycle of each group was measured by physiological system;the protein expression of phosphorylation of Akt (p-Akt),hypoxia-inducible factor-1α (HIF-1α and hemeoxygenase-1 (HO-1) was detected by Western blotting. Results The atrial pulse pressure of the HI group,ELT group,and LY294002 group at the end of 7th cycle was significantly lower than that of the NC group (all P <0. 05);the atrial pulse pressure of ELT group and LY294002 group at the end of 13th cycle was significantly higher than that of the HI group (all P < 0. 05). Furthermore,the protein level of p-Akt in the HI group was significantly lower than that of the NC group,while the protein level of the ELT group was higher than those of the HI group and LY294002 group (both P < 0. 05);the protein levels of HIF-1α and HO-1 in the HI group were significantly higher than those of the NC group,and the ELT group was higher than the HI group and LY294002 group (all P < 0. 05). Conclusion The ethanol extract of ELT has cardioprotective effect on myocardial HI of rats in vitro by up-regulating the PI3K/ Akt/ HIF-1α signaling pathway and thus promoting the HO-1 protein expression.%目的 观察泽兰乙醇提取物对大鼠离体心肌缺氧损伤的影响,并探讨其机制.方法 将40只雄性SD大鼠随机分为正常对照组、HI模型组、泽兰组和LY294002组,各10只.取各组大鼠左心房建立心房灌流模型,正常对照组用氧饱和的HEPES缓冲液进行离体灌流,其他三组制备急性心肌缺氧损伤模型,泽兰组灌流时加入泽兰乙醇提取物(0.1 mg/mL),LY294002组加入PI3K/Akt信号通路阻断剂LY294002(1.0 mol/L)、泽兰乙醇提取物(0.1 mg/mL).采用生理记录系统观察第1循环末、第7循环末、第13循环末时各组大鼠的心房搏动压,并采用Western blotting法检测各组大鼠心脏组织中磷酸化Akt(p-Akt)、缺氧诱导因子-1α(HIF-1α)、血红素氧合酶-1(HO-1)蛋白表达.结果 心房搏动压在第7循环末时HI模型组、泽兰组、LY294002组均较正常对照组低(P均<0.05),在第13循环末时泽兰组、LY294002组较HI模型组高(P均<0.05).HI模型组心肌组织中p-Akt蛋白表达较正常对照组低,泽兰组较HI模型组、LY294002组高(P均<0.05);HI模型组HIF-1α、HO-1蛋白表达均较正常对照组高,泽兰组均较HI模型组及LY294002组高(P均<0.05).结论 泽兰乙醇提取物对大鼠离体缺氧损伤心肌具有保护作用,其机制可能与上调PI3K/Akt/HIF-1α信号通路,从而增强其下游的HO-1蛋白表达有关.