陈涵,王琛,张龙岩,鄢华,苏王,江友

• 1:武汉科技大学附属武汉亚洲心脏病医院心内科

摘要(Abstract)：

目的探讨阿托伐他汀能否通过调控张力蛋白同源第10染色体丢失的磷酸酶基因(PTEN)/蛋白激酶B(Akt)降低猪冠状动脉微栓塞(CME)后心肌细胞的凋亡。方法选择12周龄健康小型猪15头,随机分为假手术组(等量生理盐水注射至冠状动脉内)、CME组、CME+阿托伐他汀组[CME建立前阿托伐他汀预处理(连续服用7 d,每日20 mg,CME前负荷80 mg]。模型建立后12 h采用超声心动图检测心功能,TUNEL染色检测心肌细胞凋亡,Western blot检测PTEN、Akt、磷酸化-Akt(p-Akt)、半胱氨酸天冬氨酸特异性蛋白酶-3(Caspase-3)、cleaved-Caspase-3表达水平。结果CME组术后12 h左心室短轴缩短率(LVFS)[(26.42±2.63)%比(42.83±2.35)%]、左心室射血分数(LVEF)[(51.34±4.23)%比(66.78±3.98)%]、心输出量(CO)[(2.62±0.38)L/min比(4.25±0.58)L/min]显著低于假手术组,而左心室舒张末期内径(LVEDD)[(40.95±1.39)mm比(32.68±1.85)mm]显著高于假手术组,差异均有统计学意义(均P<0.05)。CME+阿托伐他汀组LVEF[(58.32±5.38)%比(51.34±4.23)%]、LVFS[(32.35±3.86)%比(26.42±2.63)%]、CO[(3.50±0.47)L/min比(2.62±0.38)L/min]显著高于CME组,而LVEDD显著低于CME组[(34.82±1.69)mm比(40.95±1.39)mm],差异均有统计学意义(均P<0.05)。Western blot定量分析显示,CME组心肌细胞PTEN表达与假手术组比较,明显升高[(0.86±0.35)%比(0.25±0.12)%,P=0.034];p-Akt表达与假手术组比较,明显下降[(0.37±0.15)%比(0.92±0.27)%,P=0.032];cleaved-Caspase-3含量与假手术组比较,显著增加[(1.12±0.42)%比(0.21±0.13)%,P=0.025],差异均有统计学意义。CME+阿托伐他汀组p-Akt表达[(0.82±0.25)%比(0.37±0.15)%,P=0.033]与CME组比较,显著增加;cleaved-Caspase-3含量下降[(0.58±0.35)%比(1.12±0.42)%,P=0.042]与CME组比较,显著下降。结论阿托伐他汀预处理可明显减少CME后心肌细胞凋亡并改善心功能,其机制可能是通过调控PTEN/Akt通路来实现。

关键词(KeyWords)： 阿托伐他汀;冠状动脉;微栓塞;凋亡

Abstract:

Keywords:

基金项目(Foundation): 武汉市卫生健康科研基金资助（WX19Y13）;; 武汉市卫生计生科研基金资助（WX17Q36）;; 中国中青年临床研究基金-VG基金的资助（2017-CCA-VG-011）;; 湖北省卫生计生科研基金资助（WJ2018H0108）

作者(Author): 陈涵,王琛,张龙岩,鄢华,苏王,江友

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