红芪多糖通过调控PI3K/Akt信号通路对异丙肾上腺素所致小鼠心肌肥厚的改善作用

Effects of Hedysarum polybotys polysaccharide on isoproterenol-induced mouse myocardial hypertrophy via PI3K/Akt signaling pathway

目的研究红芪多糖对异丙肾上腺素(ISO)诱导小鼠心肌肥厚及PI3K/Akt信号通路的影响。方法50只小鼠随机分为空白组、模型组、普萘洛尔组(40 mg/kg)和红芪多糖低、高剂量组(60、120 mg/kg),每组10只,灌胃给予相应剂量药物15 d,给药1 d后皮下注射ISO 14 d进行造模。给药结束后24 h,计算小鼠心脏指数,Masson染色观察心肌组织形态变化,ELISA法检测心肌组织FFA、ATP、AMP水平,RT-qPCR法检测心肌组织ANP、BNP mRNA表达,Western blot法检测心肌组织PI3K、p-PI3K、Akt、p-Akt蛋白表达。结果与空白组比较,模型组小鼠心脏指数升高(P<0.05,P<0.01),心肌细胞肥大、胶原纤维增生,FFA水平升高(P<0.01),ATP/AMP比值降低(P<0.01),ANP、BNP mRNA表达升高(P<0.01),p-PI3K/PI3K、p-Akt/Akt蛋白表达均降低(P<0.01);红芪多糖可改善ISO诱导小鼠的各项指标(P<0.05,P<0.01),且高剂量效果更佳。结论红芪多糖对ISO诱导小鼠心肌肥厚具有改善作用,该作用可能与其提高PI3K/Akt信号通路活性有关。

AIM To study the effects of Hedysarum polybotys polysaccharide(HPS)on isoproterenol(ISO)-induced myocardial hypertrophy and PI3K/Akt signaling pathway in mice.METHODS Fifty mice were randomly divided into the blank group,the model group,the propranolol group(40 mg/kg),and the low and high dose HPS groups(60,120 mg/kg),with 10 mice in each group.The mice went on with their 15 days corresponding dosing of drugs by gavage,started their 14 d subcutaneous ISO injection for modeling after day one except those of the blank group.24 h after completion of the administration,the mice had their cardiac indices levels calculated;their myocardial morphological changes observed by Masson staining;their myocardial levels of FFA,ATP and AMP detected by ELISA;their myocardial expressions of ANP and BNP mRNA detected by RT-qPCR;and their myocardial expressions of PI3K,p-PI3K,Akt and p-Akt proteins detected by Western blot.RESULTS Compared with the blank group,the model group displayed increased cardiac indices(P<0.05,P<0.01),hypertrophic myocardial cells,proliferated collagen fibers,increased FFA level(P<0.01),decreased ATP/AMP ratio(P<0.01),increased ANP and BNP mRNA expressions(P<0.01),and decreased p-PI3K/PI3K and p-Akt/Akt protein expressions(P<0.01).H.polybotys polysaccharide improved all the indices levels in ISO-induced mice(P<0.05,P<0.01),and the high dose performed the best.CONCLUSION HPS can improve ISO-induced myocardial hypertrophy in mice,and this may be associated with its evoked PI3K/Akt signaling pathway activity.