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 mechanis...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([Ca]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([Ca]i) concentration and expressions of CaN m RNA, CnA protein, and ERK-2 m RNA, but decreased MKP-1 protein expression(P<0.05 or P<0.01). Compared with Ang Ⅱ, Evo(0.3, 3 μmol/L) significantly attenuated Ang Ⅱ-induced cardiomyocyte hypertrophy, decreased the [Ca]i concentration and expressions of CaN m RNA, CnA protein, and ERK-2 m RNA, but increased MKP-1 protein expression(P<0.05 or P<0.01). Most interestingly, Evo increased the NOS activity and NO production, and upregulated the e NOS m RNA expression(P<0.05). Conclusion: Evo significantly attenuated Ang Ⅱ-induced cardiomyocyte hypertrophy, and this effect was partly due to promotion of NO production, reduction of [Ca]i concentration, and inhibition of CaN and ERK-2 signal transduction path展开更多
基金Supported by the National Natural Science Foundation of China(No.81160528)Foundation of Administration of Traditional Chinese Medicine of Guizhou Province(No.2009-79)
文摘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([Ca]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([Ca]i) concentration and expressions of CaN m RNA, CnA protein, and ERK-2 m RNA, but decreased MKP-1 protein expression(P<0.05 or P<0.01). Compared with Ang Ⅱ, Evo(0.3, 3 μmol/L) significantly attenuated Ang Ⅱ-induced cardiomyocyte hypertrophy, decreased the [Ca]i concentration and expressions of CaN m RNA, CnA protein, and ERK-2 m RNA, but increased MKP-1 protein expression(P<0.05 or P<0.01). Most interestingly, Evo increased the NOS activity and NO production, and upregulated the e NOS m RNA expression(P<0.05). Conclusion: Evo significantly attenuated Ang Ⅱ-induced cardiomyocyte hypertrophy, and this effect was partly due to promotion of NO production, reduction of [Ca]i concentration, and inhibition of CaN and ERK-2 signal transduction path
