性别对慢性交感应激导致心脏重塑的差异研究

Gender differences in cardiac remodeling induced by chronic sympathetic activation

目的探究性别对慢性交感应激导致的心脏重塑是否存在差异。方法将小鼠随机分为四组:雄性对照组、雄性异丙基肾上腺素(ISO)组、雌性对照组、雌性ISO组。皮下注射异丙基肾上腺素ISO 10 mg/(kg·d)14 d,诱导小鼠心脏重塑模型。通过心脏重量与小鼠体重之比(HW/BW)、心脏重量与胫骨长度之比(HW/TL),评估心脏重塑大体指标;超声心动图评估小鼠心功能;HE染色检测心肌细胞横截面积,超声心动图检测舒张末期室壁厚度,用于评估小鼠心脏肥大;天狼猩红染色用于评估心脏纤维化。结果雄性ISO组与对照组相比,心体比和心胫比分别增加9.1%(P<0.05)和42.8%(P<0.001),雌性ISO组与对照组相比,心体比和心胫比分别增加12.9%(P<0.05)和9.5%(P<0.05),而与雌性ISO组相比,雄性ISO组心胫比增加了19.8%(P<0.01);雄性ISO组与对照组相比,心肌细胞横截面积增加了19.1%(P<0.0001),雌性ISO组与对照组相比,小鼠心肌细胞横截面积增加了6.9%(P<0.05),而与雌性ISO组相比,雄性ISO组心肌细胞横截面积增加了11.6%(P<0.01);与对照组相比,雄性和雌性ISO组EF值和FS值均无明显差异;雄性ISO组与对照组相比,小鼠心脏纤维化面积增加了158%(P<0.0001),雌性ISO组与对照组相比,纤维化面积增加了39.7%(P<0.05),与雌性ISO组相比,雄性ISO组心脏的纤维化面积增加了119%(P<0.0001)。结论性别对慢性交感应激导致的心脏重塑存在差异,与雌鼠相比,雄鼠更容易出现心脏肥大和心脏纤维化。

Objective To investigate whether there are gender differences in cardiac remodeling induced by chronic sympathetic activation.Methods Mice were randomly divided into four groups:male control,male isoprenaline(ISO),female control,and female ISO groups.A cardiac remodeling model was established by subcutaneous injection of ISO for 14 days.The ratio of heart weight to body weight(HW/BW)and the ratio of heart weight to tibia length(HW/TL)were used to assess cardiac remodeling;Cardiac function was assessed using echocardiography to determine diastolic left ventricular posterior wall thickness(LVPW;d).Hematoxylin and eosin staining was used to determine myocyte crosssectional area.Picric-sirius red staining was used to evaluate cardiac fibrosis.Results Compared with the control group,the HW/BW and HW/TL ratios were increased by 9.1%(P<0.05)and 42.8%(P<0.001),respectively,in the male ISO group and by 12.9%and 9.5%(all P<0.05),respectively,in the female ISO group.The increase was significantly greater in the male ISO group(19.8%,P<0.01)than in the female ISO group.Compared with the control group,the myocyte cross-sectional area in the male ISO group increased by 19.1%(P<0.0001),while that in the female ISO group increased by 6.9%(P<0.05).The increase was significantly greater in the male ISO group(P<11.6%)than in the female ISO group.There was no significant difference in cardiac function among groups.Compared with the control group,the cardiac fibrosis area of the male ISO group increased by 158%(P<0.0001)and by 39.7%(P<0.05)in the female ISO group.Compared with the female ISO group,the fibrosis area of the male ISO group increased by 119%(P<0.0001).Conclusions There are gender differences in cardiac remodeling induced by chronic sympathetic activation.Greater cardiac hypertrophy and cardiac fibrosis occur in male mice compared with female mice.