金丝桃苷预处理减轻大鼠心肌缺血再灌注损伤作用与PI3K/Akt信号通路的关系(1)
[摘要]研究金丝桃苷(hyperoside，Hyp)预处理对抗大鼠心肌缺血再灌注损伤(myocardial ischemia reperfusion injury，MIRI)的保护作用及其与PI3K/Akt信号通路的关系。通过可逆性左冠状动脉前降支结扎法建立心肌缺血再灌注模型，给予大鼠心肌缺血30 min，复灌120 min。健康雄性SD大鼠60只，随机分为5组：假手术组(Sham组)、缺血再灌组(MIRI组)、Hyp预处理组(Hyp组)、Hyp预处理联合PI3K/Akt信号通路抑制剂LY294002组(Hyp+LY组)及PI3K/Akt抑制剂组(LY组)。记录各组大鼠心脏血流动力学指标，测算心肌梗死面积和大鼠血清中丙二醛(MDA)含量、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、肿瘤坏死因子(TNF-α)及白介素-6(IL-6)活性。Western blot法检测心肌p-Akt，Akt，Bcl-2和Bax的蛋白表达。结果显示，与MIRI组比较，Hyp组大鼠心脏血流动力学指标明显改善，心肌梗死面积显著降低;血清中MDA含量和CK，CK-MB，TNF-α，IL-6活性降低，SOD，CAT和GSH-Px活性明显增强;p-Akt的蛋白表达和Akt磷酸化水平明显增强，且Bcl-2蛋白表达增强，Bax蛋白表达减弱(P<0.01)。而LY294002可显著取消Hyp的以上作用(P<0.01)。结果表明，Hyp对抗大鼠心肌缺血再灌注损伤的保护作用机制可能与其激活PI3K/Akt 信号通路，上调Bcl-2 蛋白表达，下调Bax 蛋白表达等作用有关。
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[关键词]心肌缺血再灌注损伤;金丝桃苷;预处理;PI3K/Akt信号通路
[收稿日期]2014-09-20
[基金项目]国家自然科学基金项目(30840104，81374002)
[通信作者]*韩军，副教授，博士，研究方向为心脑血管药理学，Tel：(0553)3932607，E-mail： aku110@163.com
Protective effect against myocardial ischemia reperfusion injuries induced by
hyperoside preconditioning and its relationship with
, 百拇医药 PI3K/Akt signaling pathway in rats
HAN Jun1*， XUAN Jia-li1， HU Hao-ran1， CHEN Zhi-wu2
(1.Department of Pharmacology， Third-Grade Pharmacology Laboratory of State， Administration of
Traditional Chinese Medicine， Wannan Medical College， Wuhu 241002， China;
2. School of Basic Medicine， Anhui Medical University， Hefei 230031， China)
, http://www.100md.com [Abstract]To investigate the protective effect of preconditioning with hyperoside (Hyp) against myocardial ischemia-reperfusion injury (MIRI) in rats and the role of PI3K/Akt signaling pathway. MIRI was established by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min in rats.Male SD rats were randomly divided into five groups： sham group，model group (MIRI)，Hyp preconditioning group(Hyp)，Hyp preconditioning+LY294002(a PI3K/Akt signaling pathway inhibitor) group(Hyp+LY)， and LY294002 group (LY). At the end of reperfusion， hemodynamic parameters were recorded as left ventricular systolic pressure (LVSP)， left ventricular end-diastolic pressure (LVEDP) and maximal rate of increase and decrease of left ventricular pressure (±dP/dtmax). Myocardial infarct size， the oxidative stress markers， myocardial enzymes indicators and inflammatory factors were also analyzed. The expressions of Akt， p-Akt， Bax and Bcl-2 proteins was detected by using Western blot method. The results showed that Hyp preconditioning remarkably improved cardiac constriction and relaxation function， reduced myocardial infarct size and enhanced the activities of oxidative stress markers about correlated to MIRI， such as superoxide dismutase (SOD)， catalase (CAT) and glutathione-peroxidase (GSH-Px)， and decreased the contents of malondialdehyde (MDA) as compared with MIRI group. Simultaneouly， the levels of myocardial enzymes， i.e. creatine kinase (CK) and creatine kinase MB isoenzyme (CK-MB)， and inflammatory factors， for instance tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased. Hyp pretreatment apparently restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression， increasing the levels of phosphorylation of Akt and Bcl-2 expression. These effects were inhibited by LY294002， a blocker of PI3K/Akt signaling pathway. These findings indicated that the cardioprotection of Hyp preconditioning against MIRI may be related to activating PI3K/Akt signaling pathway， upregulating the expression of Bcl-2 protein and down-regulating the expression of Bax protein., http://www.100md.com(韩军 宣佳利 胡浩然 陈志武)
, http://www.100md.com
[关键词]心肌缺血再灌注损伤;金丝桃苷;预处理;PI3K/Akt信号通路
[收稿日期]2014-09-20
[基金项目]国家自然科学基金项目(30840104，81374002)
[通信作者]*韩军，副教授，博士，研究方向为心脑血管药理学，Tel：(0553)3932607，E-mail： aku110@163.com
Protective effect against myocardial ischemia reperfusion injuries induced by
hyperoside preconditioning and its relationship with
, 百拇医药 PI3K/Akt signaling pathway in rats
HAN Jun1*， XUAN Jia-li1， HU Hao-ran1， CHEN Zhi-wu2
(1.Department of Pharmacology， Third-Grade Pharmacology Laboratory of State， Administration of
Traditional Chinese Medicine， Wannan Medical College， Wuhu 241002， China;
2. School of Basic Medicine， Anhui Medical University， Hefei 230031， China)
, http://www.100md.com [Abstract]To investigate the protective effect of preconditioning with hyperoside (Hyp) against myocardial ischemia-reperfusion injury (MIRI) in rats and the role of PI3K/Akt signaling pathway. MIRI was established by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min in rats.Male SD rats were randomly divided into five groups： sham group，model group (MIRI)，Hyp preconditioning group(Hyp)，Hyp preconditioning+LY294002(a PI3K/Akt signaling pathway inhibitor) group(Hyp+LY)， and LY294002 group (LY). At the end of reperfusion， hemodynamic parameters were recorded as left ventricular systolic pressure (LVSP)， left ventricular end-diastolic pressure (LVEDP) and maximal rate of increase and decrease of left ventricular pressure (±dP/dtmax). Myocardial infarct size， the oxidative stress markers， myocardial enzymes indicators and inflammatory factors were also analyzed. The expressions of Akt， p-Akt， Bax and Bcl-2 proteins was detected by using Western blot method. The results showed that Hyp preconditioning remarkably improved cardiac constriction and relaxation function， reduced myocardial infarct size and enhanced the activities of oxidative stress markers about correlated to MIRI， such as superoxide dismutase (SOD)， catalase (CAT) and glutathione-peroxidase (GSH-Px)， and decreased the contents of malondialdehyde (MDA) as compared with MIRI group. Simultaneouly， the levels of myocardial enzymes， i.e. creatine kinase (CK) and creatine kinase MB isoenzyme (CK-MB)， and inflammatory factors， for instance tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased. Hyp pretreatment apparently restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression， increasing the levels of phosphorylation of Akt and Bcl-2 expression. These effects were inhibited by LY294002， a blocker of PI3K/Akt signaling pathway. These findings indicated that the cardioprotection of Hyp preconditioning against MIRI may be related to activating PI3K/Akt signaling pathway， upregulating the expression of Bcl-2 protein and down-regulating the expression of Bax protein., http://www.100md.com(韩军 宣佳利 胡浩然 陈志武)