Effect of total flavonoids of Dracocephalum heterophyllum Benth on norepinephrine-induced cardiomyocyte hypertrophy in rats / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To study the effect of total flavonoids of Dracocephalum heterophyllum (TFDH),a Uygur medicine,on cardiomyocyte hypertrophy induced by norepinephrine(NE),and to provide insights into the mechanism.METHODS Cardiomyocytes of primarily cultured neonatal rats were used as models. Myocardial hypertrophy was induced by NE 2 μmol·L-1. The cells were divided into cell control group,NE 2 μmol·L-1model group,and TFDH 10,25 and 50 μmol·L-1+NE 2 umol·L-1groups.CCK-8 method was used to observe the activity of myocardial cells,while RT-PCR technique was used to detect the expression of mRNA of cardiac hypertrophy gene atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC). The internal factors were glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Confocal laser scanning was used to detect the surface area of myocardial cells and[Ca2+]i.The activity of Ca2+-ATP was measured with enzymatic reaction of fragmentation cells. The concentration of NO and the activity of NOS were determined with colorimetry. RESULTS Compared with the cell control group, cardiomyocytes were stimulated at 48 h by NE 2 μmol·L-1, which could decrease the survival rate of cardiomyocytes from(95±1)% to(78+5)%,surface area increased from (178±29)μm2to(274± 38)μm2(P<0.05),the expression of mRNA of ANP and β-MHC increased from(1.00±0.01)and(1.00± 0.02)to(2.76±0.55)and(2.69±0.31),respectively(P<0.05).The concentration of[Ca2+]iincreased from 1.00±0.12 to(1.52 ± 0.41)μmol·L-1,while the activity of Ca2+-ATP decreased from 1.01±0.14 to(0.41± 0.06)μmol·L-1(P<0.05).The concentration of NO decreased from 1.50±0.14 to(1.12±0.05)μmol·L-1,and the activity of NOS decreased from 0.86±0.06 to(0.52±0.10)μmol·L-1(P<0.05).TFDH 10,25 and 50 μmol·L-1could inhibit the decline of the survival rate,increase of the surface area and the increased expressions of mRNA of ANP and β-MHC that were induced by NE(P<0.05).At the same time,it also could inhibit the increase of the concentration of[Ca2+]i,the decreased of activity of Ca2+-ATP,and the decline of the concentration of NO and the activity of NOS (P<0.05). CONCLUSION TFDH can improve the activity of cardiomyocyte hypertrophy induced by NE, down-regutate mRNA expressions of proto oncogene ANP and β-MHC,and reduce the surface area of cardiomyocytes induced by NE.The mecha-nism may be related to promoting the release of NO and regulating the concentration of [Ca2+]iand the activity of Ca2+-ATP.