关键词: 17β-雌二醇, 血管紧张素Ⅱ, 心脏收缩, 心肌细胞, 丝裂原活化蛋白激酶

Abstract: In order to investigate the protective effect and mechanism of 17β-estradiol for the induced-inhibition on cardiac function by angiotensin Ⅱ, Langendorff perfusion apparatus was used to inject perfusion fluid with AngⅡ, E2+AngⅡ, and E2+ICI+AngⅡ into in vitro hearts of mice, where the results were recorded and the cardiac systolic parameters were compared. Differential adhesion was applied to isolate and cultivate cardiomyocytes of mastomys mice, while these cells were respectively stimulated by AngⅡ, AngⅡ+E2, and AngⅡ+E2+ICI. The proliferative statuses of these groups of cardiomyocytes were compared by MTT method and the levels of p-p38 were measured by Western Blotting. In comparison to the control group, the perfusion of AngⅡ reduced the cardiac systole and diastole, where the ratio of dP/dt and the LVDP was significantly inhibited. When compared to the control group(non-stimulated), the values of these groups were respectively reduced by 21.3%, 37.1%, and 24%(P<0.05). Application of 100 nmol/L E2 could significantly improve the reduced cardiac functions by AngⅡ. When compared to the group with AngⅡ, the LVDP and the ratio of dP/dt in the pre-perfusion group with 100 nmol/L E2 were increased by 9.4%, 40.8%, and 22.4%(P<0.05). When specific E2-receptor inhibitor, 1 μmol/L ICI182, was added along with protection by 100 nmol/L E2, it was found that the application of ICI182 could partially block the protective effect of E2. In comparison to the control group, cardiomyocytes in the group with stimulation by 100 nmol/L AngⅡ significantly showed increase[A value: (0.37±0.08) vs. (0.25±0.09), P<0.05]. And, the pre-treatment with 10 nmol/L E2 could inhibit the induced proliferation of cardiomyocytes by AngⅡ[A value: (0.27±0.02) vs. (0.37±0.08), P<0.05]. In addition, ICI182 could partially block off the anti-AngⅡ-induced proliferative effect on cardiomyocytes by E2. By comparing to the blank control group, the level of p-p38 in the stimulant group with 100 nmol/L AngⅡ greatly increased[(0.26±0.06) vs. (0.12±0.05), P<0.05]. The pre-treatment with 10 nmol/L E2 could inhibit the elevation in level of p-p38, as induced by AngⅡ[(0.13±0.07) vs. (0.26±0.06), P<0.05], while ICI182 had no significant effect to inhibit E2. Estrogen could improve the AngⅡ-induced dysfunction in cardiac systole and diastole, as well as preventing proliferation of cardiomyocytes by AngⅡ. The regulatory mechanism might involve the interference on the activation of p38-MAPK signal transduction pathway. The effect of Estrogen was partially achieved by its specific receptors.

Key words: 17β-Estradiol, Angiotensin Ⅱ, Systole, Cardiomyocytes, MAPK