Role of PI3K/Akt signaling pathway in ischemic rats underwent cardiac shock waves therapy
10.3760/cma.j.issn.0253-3758.2019.06.007
- VernacularTitle: PI3K/Akt信号通路在心脏震波治疗心力衰竭大鼠模型中的作用
- Author:
Leilei SHANG
1
;
Zhen SU
1
;
Xuejuan MA
1
;
Yanqiong WANG
2
;
Yu WANG
1
;
Qixian WANG
1
;
Ping YANG
1
Author Information
1. Department of Cardiology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
2. Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
- Publication Type:Journal Article
- Keywords:
Heart failure;
Apoptosis;
Cardiac shock wave therapy
- From:
Chinese Journal of Cardiology
2019;47(6):457-464
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of PI3K/Akt signaling pathway in ischemic rats underwent cardiac shock therapy.
Methods:Adult male Sprague Dawley (SD) rats weighing 220-250 g were used to establish a heart failure model by ligation of the left anterior descending coronary artery. Rat models were defined by echocardiographic assessment at 4 weeks post operation and heart failure rats were randomly divided into 4 groups,namely heart failure group (HF group, 9 cases),heart failure+cardiac shock waves therapy group (HF+CSWT group, 9 cases),heart failure+inhibitor(HF+LY294002 group, 9 cases),heart failure+cardiac shock waves therapy group+inhibitor (HF+CSWT+LY294002 group, 9 cases),and another 9 sham-operated SD rats served as control group (sham group, 9 cases). At 8 weeks postoperation, echocardiography was used to evaluate cardiac function in each group,myocardial infarct size was measured by TTC staining,the apoptotic index of rats cardiomyocytes were detected by TUNEL method,the myocardial mRNA expression of apoptosis-related factor was detected by real-time quantitative PCR, the protein expression levels of PI3K/Akt signaling pathway and apoptosis-related pathways were detected by Western blot.
Results:(1) Eight weeks after operation, left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly lower in HF+CSWT group than in HF group (all P<0.05), left ventricular ejection fraction (LVEF) and left ventricular shortening rate (LVFS) were significantly higher in HF+CSWT group than in HF group (all P<0.05),LVEF was significantly lower in the HF+ CSWT+ LY294002 group than in HF+ CSWT group (P<0.05). (2) Myocardial infarct size was significantly lower in the HF+ CSWT group than in HF group ((5.57 ± 0.51)% vs. (25.56 ± 0.56)%, P<0.05), which was significantly higher in the HF+CSWT+LY294002 group than in HF+CSWT group ((12.90±2.34)% vs. (5.57±0.51)%,P<0.05). (3) The cardiomyocyte apoptotic index was significantly lower in the HF+CSWT group than in the HF group ((30.25±6.12)% vs. (53.85±9.89)%,P<0.05), which was significantly higher in the HF+CSWT+LY294002 group than in the HF+CSWT group ((46.12±3.42)% vs.(30.25±6.12)%,P<0.05). (4) The myocardial mRNA expression of Bcl-2 was significantly higher, while myocardial mRNA Bax and Caspase-3 expression were significantly lower in HF+CSWT group than in HF group and HF+CSWT+LY294002 group (all P<0.05). (5) The expression levels of p-Akt, Bcl-2 and pro-Caspase-3 in myocardial tissue were significantly higher in the HF+CSWT group than in the HF group and HF+CSWT+LY294002 group (all P<0.05), which were significantly lower in the HF+LY294002 group than in the HF and HF+CSWT+LY294002 groups (all P<0.05). Myocardial Bax protein expression was significantly lower in the HF+CSWT group than in the HF group and the HF+CSWT+LY294002 group (all P<0.05), which was significantly higher in the HF+LY294002 group than in the HF group (P<0.05).
Conclusion:CSWT improves cardiac function and inhibits cardiomyocyte apoptosis through PI3K/Akt signaling pathways in this rat HF model.