目的 探讨三七总皂苷（Panax notoginsenosides，PNS）调节能量代谢干预心肌细胞肥大的效应和机制。方法 采用异丙肾上腺素（Isoprenaline，ISO）诱导原代心肌细胞肥大模型，探讨PNS干预心肌细胞肥大的效应及能量代谢相关机制。将新生乳鼠心脏进行心肌细胞分离培养，随机分为正常组、ISO模型组、PNS低剂量组及PNS高剂量组。正常组和ISO模型组给予生理盐水；PNS低、高剂量组分别给予50 μg/mL及200 μg/mL PNS；孵育30 min后，ISO模型组和PNS低、高剂量组给予10 μmol/L ISO，正常组给予等体积生理盐水。培养72 h后，测定各组心肌细胞横截面积，ATP含量及脑钠肽（Brain natriuretic peptide，BNP）、过氧化物酶体增殖物激活受体-δ（peroxisome proliferators-activated receptors-δ，PPAR-δ）、长链酰基辅酶A脱氢酶（Long chain acyl-CoA dehydrogenase,LCAD）、中链酰基辅酶A脱氢酶（Medium chain acyl-COA dehydrogenase,MCAD）等基因表达水平、PPAR-δ蛋白表达及miRNA-199a表达水平。结果 与正常组比较，ISO模型组心肌细胞横截面积显著增大，ATP水平显著降低，miRNA-199a表达及BNP mRNA表达水平显著上调，PPAR-δ、LCAD、MCAD mRNA表达水平显著下调，PPAR-δ蛋白水平显著下调；与ISO模型组比较，PNS低、高剂量组心肌细胞横截面积显著减小，ATP水平显著升高，miRNA-199a表达及BNP mRNA表达水平显著下调，LCAD、MCAD mRNA表达水平显著上调，PPAR-δ蛋白水平显著上调。结论 PNS具有显著直接抑制心肌细胞肥大的效应；PNS干预MiR-199a/PPAR-δ调控、改善心肌能量代谢可能是其抑制心肌细胞肥大的作用机制之一。

Objective The current study aimed to illustrate the effect of Panax notoginsenosides (PNS) on cardiac hypertrophy. Meanwhile, the implication of energy metabolism in PNS-mediated anti-hypertrophic effects was investigated. Methods Primary cardiomyocytes were isolated from neonatal rats and subject to Isoprenaline (ISO) incubation to induce cardiac hypertrophy. Isolated cardiomyocytes were randomly divided into the experimental groups including normal control group, ISO-challenged group, ISO-challenged and low-dose PNS treatment group (PNSL) and ISO-challenged and PNS high-dose treatment group (PNSH). The PNS was administered at 50 μg/mL and 200 μg/mL, respectively. The normal group and the ISO-challenged group were given saline solution in the same volume. Thirty minutes after the incubation, ISO group and the PNS-treated groups were given ISO at 10 μmol/L. The normal control group was given the same amount of saline solution. After 72 h incubation, the cross-sectional area (CSA) of cardiomyocytes, ATP level, the mRNA expression of brain natriuretic peptide (BNP), peroxisome proliferators-activated receptors-δ (PPAR-δ), long chain acyl-CoA dehydrogenase (LCAD) and medium chain acyl-COA dehydrogenase (MCAD), the protein level of PPAR-δ protein and the expression level of miRNA-199a were examined.Results Compared to that from the normal control group, the CSA of cardiomyocytes was significantly increased in the ISO-challenged group. Meanwhile, the level of ATP was significantly decreased in the ISO-challenged group. The expression level of miRNA-199a and the mRNA expression of BNP were significantly up-regulated in ISO-challenged group. The mRNA expression level of PPAR-δ, LCAD and MCAD was significantly down-regulated in ISO-challenged group. The protein level of PPAR-δ was significantly decreased in ISO-challenged group. Compared to that from the ISO-challenged group, the CSA of cardiomyocytes in PNS group was significantly reduced. Moreove, the level of ATP was significantly increased in PNS group. The expression levels of miRNA-199a and BNP were significantly down-regulated in PNS group. The mRNA expression levels of LCAD and MCAD were significantly up-regulated in PNS group. The protein level of PPAR-δ was significantly increased in PNS group.Conclusion PNS directly attenuates ISO-induced cardiomyocyte hypertrophy in part through increasing ATP level in the cardiomyocytes. In addition, targeted regulation of MiR-199a/PPAR-δ is involved in the anti-hypertrophic effect of PNS in the cardiomyocytes.

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