黄芪甲苷对异丙肾上腺素诱导大鼠心肌肥厚及过氧化物酶体增殖活化受体γ辅助活化因子1α的影响

Effect of astragaloside IV on myocardial hypertrophy and PGC-1α induced by isoproterenol in rats

目的:探讨黄芪甲苷(Astragaloside IV,As IV)对异丙肾上腺素(ISO)诱导大鼠心肌肥厚及过氧化物酶体增殖活化受体γ辅助活化因子1α(PGC-1α)的影响。方法:60只雄性大鼠分别于ISO造模前一天给予等体积黄芪甲苷(20、40、80 mg/kg/d)、普萘洛尔(40 mg/kg/d)或羧甲基纤维素钠(0.05%)灌胃,第2天同时皮下注射ISO(5 mg/kg/d),持续造模2周。通过全心质量指数(HMI)、左心质量指数(LVMI)观察心肌肥厚程度;苏木精-伊红(HE)染色法观察心脏组织形态学改变;:酶联免疫吸附测定(Elisa)检测三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、单磷酸腺苷(AMP)及游离脂肪酸(FFA)的表达水平;逆转录-聚合酶链反应(RT-PCR)检测心肌组织心房钠尿肽(ANP)mRNA表达水平;蛋白免疫印迹(Western blot)检测心肌组织PGC-1α的蛋白表达水平。结果:ISO组大鼠心肌明显肥厚,HMI、LVMI及ANP mRNA的表达水平明显增加。与ISO组相比,黄芪甲苷40、80 mg/kg/d剂量组ATP/AMP、ATP/ADP比值,PGC-1α蛋白表达水平均增加;FFA含量减少。结论:黄芪甲苷可能通过过氧化物酶体增殖活化受体γ辅助活化因子1α改善异丙肾上腺素诱导的心肌肥厚能量代谢水平表达,发挥心肌保护作用。

Objective： To explore the effect of of Astragaloside IV on myocardial hypertrophy and PGC-1α in rats induced by isoproterenol（ ISO）.Methods： Male Sprague-Dauley（ SD） rats were treated with astragalosides and propranolol by intragastric（ ig） administration respectively,at a dose of 20,40,80 mg /kg /day and 40 mg /kg /day one day prior to isoproterenol or vehicle（ 5 mg /kg /day,sc） for 2 week. At the end of the treatment period,HMI,LVMI and pathological section by HE staining were observed. ATP,ADP,AMP and FFA levels were detected by Elisa; The expression of ANP mRNA were determined by RT-PCR; The expression of PGC-1α were assessed by Western blot. Results： ISO model group markedly elevated the left ventricle weight（ LVW） / body weight（ BW）,heart weight（ HW） /body weight（ BW） ratio and ANP mRNA level. Compared with ISO group,treatment with ASIV（ 40,80 mg /kg /d） significantly improved ATP /AMP,ATP /ADP ratio and PGC-1α protein expression and reduced the accumulation of free fatty acid. Conclusions： ASIV may alleviate metabolism by regulating PGC-1α axis and protect ISO-induced cardiac hypertrophy.