番石榴叶总黄酮对AngII诱导的乳鼠心肌细胞肥大的抑制作用及机制.

Objective To investigate the inhibitory effect and mechanism of total flavones from Psidium guajava leaves on cardiomyocyte hypertrophy induced by angiotensin II(AngII) in vivo of neonatal mice. Methods The cardiomyocytes isolated from neonatal Wistar rats were cultured in vitro and divided into the model group and low-, medium-and high-dose groups of total flavonoids from Psidium guajava leaves, meanwhile, we set up the normal control group. AngII 0. 1 μmol/L was added to the model group to induce cardiomyocyte hypertrophy. The cells in the low-, medium-and high-dose groups of total flavonoids from Psidium guava leaves were first pretreated with 50, 100, and 150 μg/m L total flavonoids from Psidium guajava leaves for 24 h, and then cultured with AngII 0. 1 μmol/L for 24 h. The cells in the normal control group were first cultured in DMEM high sugar medium containing 10% FBS for 24 h, then received the serum-free culture with DMEM containing 0. 1% FBS for 48 h. Cell area was measured by immunofluorescence staining. The total protein content of myocardial cells of each group was detected with Bradford method. The expression of angiotensin II type 1 receptor(AT1 R)and protein kinase C(PKC) was detected by Western blotting. Results Compared with the normal control group, the area of myocardial cells in the model group and low-, medium-and high-dose groups increased; compared with the model group, the area of myocardial cells in the low-, medium-and high-dose groups decreased; and the area of myocardial cells in the high-dose group was smaller than that in the low-and medium-dose group(all P<0. 01). Compared with the control group, the total protein content in the myocardial cells of the model group increased(P<0. 01). Compared with the model group, the total protein content of guava leaf flavonoids in each dose group decreased, and the high-dose group was less than the medium-and low-dose groups(all P<0. 05). Compared with the normal control group, the expression of AT1 R and PKC of the model group increased(both P<0. 01). Compared with the model group, the expression of AT1 R and PKC in different dosage groups decreased(all P<0. 01). Conclusion AngII can induce the cardiomyocyte hypertrophy in the neonatal mice, and pretreatment with total flavonoids from Psidium guajava leaves can inhibit the increase of cell size and protein synthesis, and thus inhibit cardiomyocyte hypertrophy, which is related to the regulation of AT1 R-PKC pathway. [ABSTRACT FROM AUTHOR]