PPAR-α/NO Signaling Pathway Involves In The Effects Of Berberine On Anti-cardiomyocyte Hypertrophy Induced By Angiotensin Ⅳ

Objective: To investigate the role and the mechanisms of berberine on cardiomyocyte hypertrophy induced by angiotensinⅣ(AngⅣ)and its possible effects on peroxisome proliferator-activated receptor-α(PPAR-α)/nitric oxide (NO) signal pathway.Methods: The cardiomyocyte hypertrophic responses were analyzed by detecting the atrial natriuretic factor (ANF) mRNA expression,protein content and cell surface area. The mRNA expressions of cardiomycytes were analyzed by real time RT-PCR. The protein expressions were measured by Western blot. The NO concentration and nitric oxide synthase (NOS) activity were determined by using the spectrophotometry and nitrate reduction methods, respectively.Results: In cultured cardiomyocytes, AngⅣ(0.01,0.1, 1 nM) significantly induced cardiomyocyte hypertrophy,ANF mRNA expression, protein content and the cell surface area were increased in a concentration-dependent manner. AngⅣat 1 nM decreased the mRNA expressions of PPAR-αand eNOS, also decreased the protein expressions of PPAR-α(P<0.01) and the NOS activity (P<0.01), and reduced NO concentration, too (P<0.01). Berberine (10,30,100μM) significantly depressed cardiomyocyte hypertrophy induced by AngⅣat 1 nM in a concentration-dependent manner. Berberine at 30μM upregulated the mRNA expressions of PPAR-αand eNOS , increased the protein expressions of PPAR-αand NOS activity, as well as NO concentration,the effect of fenofibrate and L-arginine were same to berberine (P<0.01). The effects of berberine and fenofibrate were abolished by PPAR-αantagonist MK 886 (P<0.01), and the effects of L-arginine and berberine could be blocked by NOS inhibitor NG-nitro-L-arginine- methyl ester (P<0.01).Conclusions: 1) PPAR-α/NO signal pathway involves in the effects of cardiomyocyte hypertrophy induced by AngⅣ. 2) Berberine has an inhibition effect on cardiomyocyte hypertrophy induced by AngⅣ, which the underlying mechanism may be mediated by activating the expression of PPAR-α, and then upregulating the mRNA expression of eNOS,elevating the activity of NOS, and finally, increasing the release of NO.