科研之友
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摘要
Objective: To investigate the effects of evodiamine(Evo), a component of Evodiaminedia rutaecarpa(Juss.) Benth, on cardiomyocyte hypertrophy induced by angiotensin Ⅱ(Ang Ⅱ) and further explore the potential mechanisms. Methods: Cardiomyocytes from neonatal Sprague Dawley rats were isolated and characterized, and then the cadiomyocyte cultures were randomly divided into control, model(Ang Ⅱ 0.1 μmol/L), and Evo(0.03, 0.3, 3 μmol/L) groups. The cardiomyocyte surface area, protein level, intracellular free calcium([Ca2+]i) concentration, activity of nitric oxide synthase(NOS) and content of nitric oxide(NO) were measured, respectively. The m RNA expressions of atrial natriuretic factor(ANF), calcineurin(CaN), extracellular signal-regulated kinase-2(ERK-2), and endothelial nitric oxide synthase(e NOS) of cardiomyocytes were analyzed by real-time reverse transcriptionpolymerase chain reaction. The protein expressions of calcineurin catalytic subunit(CnA) and mitogen-activated protein kinase phosphatase-1(MKP-1) were detected by Western blot analysis. Results: Compared with the control group, Ang Ⅱ induced cardiomyocytes hypertrophy, as evidenced by increased cardiomyocyte surface area, protein content, and ANF m RNA expression; increased intracellular free calcium([Ca2+]i) concentration and expressions of CaN m RNA, CnA protein, and ERK-2 m RNA, but decreased MKP-1 protein . Compared with Ang Ⅱ, Evo(0.3, 3 μmol/L) significantly attenuated Ang Ⅱ-induced cardiomyocyte hypertrophy, decreased the [Ca2+]i concentration and expressions of CaN m RNA, CnA protein, and ERK-2 m RNA, but increased MKP-1 protein . Most interestingly, Evo increased the NOS activity and NO production, and upregulated the e NOS m RNA . Conclusion: Evo significantly attenuated Ang Ⅱ-induced cardiomyocyte hypertrophy, and this effect was partly due to promotion of NO production, reduction of [Ca2+]i concentration, and inhibition of CaN and ERK-2 signal transduction pathways.
