【摘要】 目的：观察钙调神经磷酸酶（ｃａｌｃｉｎｅｕｒｉｎ，ＣａＮ）依赖的信号通路在大鼠心肌肥大中的作用。方法：通过腹主动脉缩窄复制大鼠压力超荷性心肌肥大模型，观察ＣａＮ特异性抑制剂环孢素Ａ（ｃｙｃｌｏｓｐｏｒｉｎ Ａ，ＣｓＡ）对大鼠心系数以及血浆及心肌组织心钠素（ａｒｉｔｒｉａｌｎａｔｒｉｕｒｅｔｉｃ ｐｅｐｔｉｄｅ，ＡＮＰ）水平的影响。同时，在培养的大鼠心肌细胞及心脏成纤维细胞上，观察ＣｓＡ 对血管紧张素Ⅱ（ａｎｇｉｏｔｅｎｓｉｎ Ⅱ， ＡｎｇⅡ） 刺激的３Ｈ亮氨酸及３Ｈ胸腺嘧啶参入的影响。结果：腹主动脉缩窄大鼠心系数较假手术组增高３８％ （ Ｐ＜ ０．０１） 。应用ＣｓＡ 治疗的大鼠心系数下降了８５％ （ Ｐ＜０ ．００１）。同时，观察到腹主动脉缩窄大鼠心肌组织及血浆ＡＮＰ含量较对照组分别增高１３５ ％ 和１１７ ％ （Ｐ＜ ０ ．０１） ，ＣｓＡ 处理后，ＡＮＰ分别下降了１６ ％ 和１４％ 。在培养的大鼠心肌细胞及心脏成纤维细胞上，观察到ＣｓＡ（０ ．１ ～１０μｍｏｌ·Ｌ－１）可以浓度依赖的方式抑制血管紧张素Ⅱ刺激的３Ｈ亮氨酸及３Ｈ胸腺嘧啶参入的增加。结论：ＣａＮ 依赖的信号通路可能参与了压力超负荷及血管紧张素Ⅱ诱导的大鼠心?更多还原

【Abstract】 Objective: To determine the role of calcineurin dependent signal pathway in cardiac hypertrophy of rats. Methods: The rat model of pressure overload induced cardiac hypertrophy was produced by constriction of the abdominal aorta. The heart/body weight ratio and the atrial natriuretic peptide (ANP) levels in plasma and heart tissues of rats were investigated. The primary cardiac myocytes and fibroblasts were cultured under the standard conditions. Protein/DNA synthesis rate was assessed by 3H Leucine/ 3H TdR incorporation. Results: The heart/body weight ratio of each rat with abdominal aorta constriction was increased by 38% compared with that of the sham operated group, and cyclosporin A (CsA) treatment decreased 85%. The ANP levels in plasma and heart tissues of rats with abdominal aorta constriction were signicantly increased by 135% and 117% respectively, compared with that in the sham operated group, which was slightly reduced by CsA treatment. CsA(0.1 10 umol·L -1 ) decreased protein synthesis rate in AngⅡ treated cardiomyocytes and DNA synthesis rate in AngII treated fibroblasts in a dose dependent manner. Conclusion: Calcineurin dependent signal pathway may involve in pressure overload and AngII induced cardiac hypertrophy.更多还原