黄芪多糖通过调控PGC-1α抑制异丙肾上腺素诱导的大鼠心肌肥厚
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国家自然科学基金资助(30973898/C190702);辽宁省自然科学基金资助(201102141)


Astragalus Polysaccharides Protect Cardiac Hypertrophy Induced by ISO via PGC-1α Signaling Pathway
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    摘要:

    目的 探讨黄芪多糖(APS)对异丙肾上腺素(ISO)诱导心肌肥厚中能量代谢的影响。方法 以ISO 15 mg/(kg·d)腹腔注射制备大鼠心肌肥厚模型。60只SD大鼠随机分为6组,每组10只:对照组、ISO组、ISO+APS 200 mg/(kg·d)组、ISO+APS 400 mg/(kg·d)组、ISO+APS 800 mg/(kg·d)组、ISO+普萘洛尔40 mg/(kg·d)组。APS 200、400、800 mg/(kg·d)及普萘洛尔40 mg/(kg·d)组连续腹腔注射所对应药物3周,并在注射药物一天后腹腔注射ISO 2周。在给药3周后,分别检测大鼠心脏质量指数(HMI)、左心室质量指数(LVMI)、左心室舒张期末压(LVEDP)、左心室收缩压(LVSP),取左心室组织进行HE染色,测量左心室心肌细胞横径(TDM);RT-PCR检测心肌组织心房钠尿因子(ANF)、过氧化体增殖物激活型受体γ共激活因子1α(PGC-1α) mRNA的表达;Western blot检测心肌组织PGC-1α的蛋白表达;ELISA检测血清中游离脂肪酸(FFA)、AMP、ADP、ATP的含量。结果 与对照组相比,ISO组大鼠表现为HMI和LVMI显著增加,LVEDP增大,LVSP降低,ANF mRNA 表达增加,PGC-1α蛋白含量减少,FFA升高,ATP/ADP、ATP/AMP比值明显降低。与ISO组相比,APS不同剂量组表现为HMI和LVMI降低,LVDEP降低,LVSP升高,ANF mRNA 表达减少,PGC-1α蛋白含量增加,FFA降低,ATP/ADP、ATP/AMP比值增加,且呈一定的剂量依赖性。结论 APS能改善ISO诱导的心肌肥厚,其机制可能是调控PGC-1α来提高能量代谢保护心脏。

    Abstract:

    Aim To explore the effect of astragalus polysaccharides (APS) on myocardial hypertrophy in rats induced by isoproterenol (ISO). Methods 15 mg/(kg·d) ISO were used as myocardial hypertrophy models by intraperitoneally injection. 60 SD rats were randomly assigned to six groups, 10 rats for each group: the control group, ISO group, ISO+APS 200 mg/(kg·d) group, ISO+APS 400 mg/(kg·d) group, ISO+APS 800 mg/(kg·d) group and ISO+propranolol 40 mg/(kg·d) group. Administered groups were continually intraperitoneally injected administration for 3 weeks, and ISO were intraperitoneally injected as long as 2 weeks in the day after that. After 3 weeks, at the end of the treatment period, hemodynamic parameters were observed, and pathological section by HE staining. The expression of free fatty acid (FFA), ATP, ADP, AMP were quantified by ELISA. The expression of atrial natriuretic factor (ANF), PGC-1α mRNA were determined by RT-PCR, the expression of PGC-1α protein were determined by Western blot in the tissue. Results Compared with control group, ISO group markedly elevated HMI, LVMI, LVEDP level and decreased LVSP level, meanwhile the expression of ANF mRNA were increased and the expressions of PGC-1α mRNA and protein decreased. Compared with ISO group, the APS for different dose groups dependently improved hemodynamic parameters, ATP/AMP and ATP/ADP ratio and PGC-1α mRNA and protein expressions. Conclusions APS can improve cardiac hypertrophy induced by ISO, which maybe improve energy metabolism by PGC-1α.

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栾爱娜,王洪新,张英杰,张素萍,鲁美丽,梅 蒙,许崇华.黄芪多糖通过调控PGC-1α抑制异丙肾上腺素诱导的大鼠心肌肥厚[J].中国动脉硬化杂志,2014,22(06):547~552.

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  • 收稿日期:2014-01-26
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