Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
Int J Biol Sci. 2011 Apr 7;7(3):383-9. doi: 10.7150/ijbs.7.383.
Pathological cardiac hypertrophy induced by adrenergic overactivation can subsequently develop to heart failure which remains as a leading cause of mortality worldwide. Tanshinone IIA is a lipid-soluble pharmacologically active compound extracted from the rhizome of the Chinese herb Salvia miltiorrhiza, a well-known traditional Chinese medicine used for the treatment of cardiovascular disorders. However, little is know about the effect of Tanshinone IIA on cardiac hypertrophy. The present study was aimed to investigate whether Tanshinone IIA prevents cardiac hypertrophy induced by isoproterenol (ISO) and to clarify its possible mechanisms. Cardiomyocytes hypertrophy was induced by ISO 10 μM for 48 h with or without Tanshinone IIA 10, 30, 100 μM pretreatment, and evaluated by determining the cell size and the expression of ANP, BNP, β-MHC, Calcineurin, and NFATc3 by real-time PCR and western blot. We found that Tanshinone IIA pretreatment attenuated the enlargement of cell surface area induced by ISO in cultured cardiomyocytes. The mRNA level of ANP, BNP and β-MHC was obviously elevated in ISO-treated cardiac cells, which was effectively inhibited by Tanshinone IIA. Moreover, we found that Tanshinone IIA pretreatment could prevent the augment of intracellular calcium transient in ISO-treated cardiomyocytes. The further study revealed that Calcineurin, NFATc3, ANP, BNP and β-MHC proteins were upregulated by ISO in ventricular myocytes, and Tanshinone IIA pretreatment significantly attenuate the increased expression of Calcineurin, NFATc3, ANP, BNP and β-MHC proteins. In summary, Tanshinone IIA attenuated cardiomyocyte hypertrophy induced by ISO through inhibiting Calcineurin/NFATc3 pathway, which provides new insights into the pharmacological role and therapeutic mechanism of Tanshinone IIA in heart diseases.
儿茶酚胺过度激活诱导的病理性心肌肥厚可随后发展为心力衰竭，这仍然是全球死亡的主要原因。丹参酮 IIA 是一种脂溶性的具有药理活性的化合物，从丹参的根茎中提取而来，丹参是一种著名的中草药，用于治疗心血管疾病。然而，关于丹参酮 IIA 对心肌肥厚的影响知之甚少。本研究旨在探讨丹参酮 IIA 是否预防异丙肾上腺素（ISO）诱导的心肌肥厚，并阐明其可能的机制。用 10 μM ISO 预处理 48 小时诱导心肌细胞肥大，并用或不用 10、30、100 μM 丹参酮 IIA 预处理，通过实时 PCR 和 Western blot 测定细胞大小和 ANP、BNP、β-MHC、钙调神经磷酸酶和 NFATc3 的表达来评估。结果发现，丹参酮 IIA 预处理可减轻 ISO 诱导的培养心肌细胞表面积增大。ISO 处理的心肌细胞中 ANP、BNP 和 β-MHC 的 mRNA 水平明显升高，而丹参酮 IIA 可有效抑制其升高。此外，我们发现丹参酮 IIA 预处理可防止 ISO 处理的心肌细胞内钙瞬变的增加。进一步的研究表明，ISO 在心室肌细胞中上调钙调神经磷酸酶、NFATc3、ANP、BNP 和 β-MHC 蛋白，而丹参酮 IIA 预处理可显著减轻钙调神经磷酸酶、NFATc3、ANP、BNP 和 β-MHC 蛋白的表达增加。总之，丹参酮 IIA 通过抑制钙调神经磷酸酶/NFATc3 通路减轻 ISO 诱导的心肌细胞肥大，为丹参酮 IIA 在心脏病中的药理作用和治疗机制提供了新的见解。
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