天津医药

天津医药 ›› 2018, Vol. 46 ›› Issue (1): 16-19.doi: 10.11958/20170878

• 实验研究 • 上一篇    下一篇

美托洛尔对腹主动脉缩窄大鼠心肌 CalpainⅠ、 CaN 信号通路的影响

姚健 1，朱健华 2，盛红专 2△   

  1. 1 南通大学医学院组胚教研室（邮编 226001）；2 南通大学附属医院心内科
  • 收稿日期:2017-08-08 修回日期:2017-10-31 出版日期:2018-01-15 发布日期:2018-01-16
  • 通讯作者: 盛红专 E-mail:247173878@qq.com
  • 作者简介:姚健（1969），男，博士，副教授，主要从事心脏重构的分子生物学研究
  • 基金资助:
    心室CaMK II信号转导通路调控慢性心衰室性心律失常的机制;多个系统基因多态性在高血压病、肥厚型心肌病患者中的分布特征及对心肌肥厚的影响

The effect of metoprolol on Calpain I and CaN signaling pathway in pressure overload induced myocardial hypertrophy

YAO Jian1, ZHU Jian-hua2, SHENG Hong-zhuan2△   

  1. 1 Department of Histology and Embryology, Medical School of Nantong University, Nantong 226001, China; 2 Department of Cardiology, the Affiliated Hospital of Nantong University
  • Received:2017-08-08 Revised:2017-10-31 Published:2018-01-15 Online:2018-01-16
  • Contact: Hong-Zhuan SHENG E-mail:247173878@qq.com

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摘要： 目的 以钙调神经磷酸酶（CaN）和钙蛋白酶Ⅰ（Calpain Ⅰ）为研究对象，探讨美托洛尔预防腹主动脉缩窄 大鼠心肌肥厚的机制。方法 30 只 SD 大鼠建立腹主动脉缩窄模型，造模成功者随机分为假手术组（n=10）、腹主动 脉缩窄手术组（n=9）和美托洛尔组（n=9，在腹主动脉缩窄基础上每日予美托洛尔干预）。术后 4 周检测大鼠血压［收 缩压（SBP）/舒张压（DBP）］及心肌肥厚程度变化［左心室质量/体质量的比值（LVW/BW 表示）］，逆转录 PCR（RTPCR）法检测 CaN mRNA 表达，Western blot 法检测 CaN 和 CalpainⅠ蛋白表达。检测各组的 CaN 酶活性。结果 手 术组大鼠 SBP、DBP、LVW/BW，心肌 CaN mRNA、CaN 蛋白、CaN 活性及 CalpainⅠ蛋白表达均较假手术组增高（P＜ 0.05）。美托洛尔组大鼠 SBP、DBP 虽较手术组略下降，但差异无统计学意义（P＞0.05），且仍高于假手术组（P＜ 0.05）。与手术组相比，美托洛尔组大鼠 LVW/BW、心肌中 CaN mRNA、蛋白表达和酶活性，CalpainⅠ蛋白显著下降 （P＜0.05），与假手术组差异均无统计学意义。结论 美托洛尔可通过抑制 CalpainⅠ，调控 CaN 信号通路，从而预防 压力超负荷大鼠心肌肥厚的发生。

关键词: 主动脉缩窄, 美托洛尔, 大鼠, Sprague-Dawley, 钙蛋白酶 Ⅰ, 钙调神经磷酸酶, 心肌肥厚

Abstract: Objective To study the mechanism of metoprolol preventing pressure overload induced myocardial hypertrophy through inhibiting calcineurin (CaN) and Calpain Ⅰ signaling pathway in rat model of coarctation of abdominal aorta. Methods Thirty SD rats were used for hypertension rat model induced by coarctation of suprarenal abdominal aorta. Model rats were divided into three groups, sham operation group (n=10), abdominal aortic coarctation group (n=9) and metoprolol group (n=9). The changes of blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] and myocardial hypertrophy [the ratio of left ventricular mass / body mass (LVW/BW)] were measured. RT-PCR was used to detect the expression of CaN mRNA, and Western blot assay was used to detect expressions of CaN and Calpain Ⅰ proteins. The activity of CaN enzyme was detected and compared between three groups. Results Compared with the sham-operated sham operation group, values of SBP, DBP, LVW/BW, protein expressions and activities of CaN mRNA, CaN and Calpain Ⅰ were significantly increased in operation group (P＜0.05). There were no significant differences in SBP and DBP between metoprolol-treated group and the operation group (P＞0.05). Furthermore, values of SBP and DBP were significantly higher in metoprolol-treated group than those of sham group (P＜0.05). Compared with operation group, values of LVW/BW, the protein expression and activity of CaN mRNA and Calpain Ⅰ were significantly decreased in metoprolol group (P＜0.05), which were no significant differences compared with sham group. Conclusion Metoprolol prevents myocardial hypertrophy in abdominal aorta coarctative rats, through inhibiting Calpain Ⅰ and CaN signaling pathways.

Key words: aortic coarctation, metoprolol, rats, sprague-dawley, calpain Ⅰ, calcineurin, myocardial hypertrophy