摘要
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。
Objective To investigate whether atorvastatin can reduce the apoptosis of myocardial cells after porcine coronary microembolization by regulating phosphatase and tensin homolog deleted on chromosome ten(PTEN)/Akt pathway. Methods Fifteen swine were randomly and equally assigned into sham-operated(control) group, coronary microembolization(CME) group and atorvastatin group. CME was induced by injection of microspheres selectively into left anterior descending artery;for control group, the same dose of normal saline was substituted for microspheres;and those in atorvastatin group were pretreated with 20 mg/day for 7 days, the use of 80 mg load 60 minutes before microspheres injection. Cardiac function was assessed by echocardiography,cardiomyocyte apoptosis was detected by TUNEL staining,and the expression level of PTEN,Akt,p-Akt,caspase-3 were measured by Western blot 12 h after operation. Results Compared with sham-operated group, cardiac function was signifi cantly decreased in CME group(P<0.05);However, cardiac function was signifi cantly improved in atorvastatin group compared with CME group(P<0.05). Compared with control group, myocardial apoptosis rate and the levels of activated caspase-3 increased significantly in CME group(P<0.05). Again, these effects were ameliorated by atorvastatin(P<0.05). Conclusions Pretreatment with atorvastatin can significantly reduce cardiomyocyte apoptosis and improve cardiac function after CME, and its mechanism may be achieved by regulating the PTEN/Akt pathway.
作者
陈涵
王琛
张龙岩
鄢华
苏王
江友
CHEN Han;WANG Chen;ZHANG Long-yan;YAN Hua;SU Xi;WANG Jiang-you(Department of Cardiology,Wuhan Asian Heart Hospital Affiliated to Wuhan University of Science and Technology,Wuhan 430022,China)
出处
《中国介入心脏病学杂志》
2019年第12期700-706,共7页
Chinese Journal of Interventional Cardiology
基金
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）
关键词
阿托伐他汀
冠状动脉
微栓塞
凋亡
Atorvastatin
Coronary artery
Microembolization
Apoptosis
