Role of exosomes in propofol-induced elimination of cardioprotective effect of remote ischemic preconditioning in rats
10.3760/cma.j.cn131073-20240914-00808
- VernacularTitle:外泌体在丙泊酚消除大鼠远端缺血预处理心肌保护效应中的作用
- Author:
Shuai QIN
1
;
Aoxue LI
1
;
Min WANG
1
;
Xinzhe WU
1
;
Yun WU
1
Author Information
1. 安徽医科大学第二附属医院麻醉与围术期医学科 麻醉与围术期医学安徽普通高校重点实验室（安徽医科大学），合肥 230601
- Publication Type:Journal Article
- Keywords:
Exosomes;
Propofol;
Ischemic preconditioning;
Myocardial reperfusion injury
- From:
Chinese Journal of Anesthesiology
2025;45(8):959-965
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of exosomes in propofol-induced elimination of cardioprotective effect of remote ischemic preconditioning (RIPC) in rats.Methods:This experiment was performed in 2 parts. In vivo experiment Forty-eight healthy SPF male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 5 groups using the random number table method: sham operation group (Sham group, n=12), ischemia-reperfusion (I/R) group ( n=12), RIPC group ( n=8), RIPC+ propofol group (RIPC+ P group, n=8), and propofol+ I/R group (P+ I/R group, n=8). The model of myocardial I/R injury was developed by ligating the left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion in anesthetized animals. Four cycles of 5-min ischemia induced by occlusion of the bilateral hind limbs with a tourniquet/5-min reperfusion served as the RIPC stimulus. Propofol was intravenously infused at a rate of 12 mg·kg -1·h -1 in RIPC+ P group (during RIPC) and in P+ I/R group (for 40 min). Exosomes from RIPC-treated and RIPC+ propofol-treated rats were extracted (RIPC-EXO and RIPC+ P-EXO respectively) for determination of the expression of surface markers of exosomes CD9 and HSP70. Another 24 rats were randomly selected, and the aforementioned exosomes were injected at 15 min before myocardial ischemia, resulting in RIPC-EXO+ I/R group ( n=12) and RIPC+ P-EXO+ I/R group ( n=12). At the end of reperfusion, the area of myocardial infarction was determined, the concentration of serum cardiac troponin I (cTnI) was measured by the enzyme-linked immunosorbent assay, and the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in myocardial tissues was detected by Western blot. Cell experiment H9c2 cells were cultured in vitro and divided into 4 groups ( n=6 each) using a random number table method: control group (C group), hypoxia-reoxygenation group (H/R group), RIPC-EXOc group and RIPC+ P-EXOc group. The cells were exposed to hypoxia for 4 h followed by reoxygenation for 16 h in H/R group. RIPC-EXO and RIPC+ P-EXO were added at a final concentration of 300 μg/ml before hypoxia in RIPC-EXOc group and RIPC+ P-EXOc group, respectively. The cell viability was determined using a cell counting kit-8 assay and the expression of Bax and Bcl-2 expression was detected by Western blot. Results:In vivo experiment Compared with RIPC-EXO group, the expression of CD9 and HSP70 was significantly down-regulated in RIPC+ P-EXO group ( P<0.05). Compared with Sham group, the percentage of the area of myocardial infarction was significantly increased, and the serum cTnI concentration and Bax/Bcl-2 ratio in myocardial tissues were increased in I/R group ( P<0.05). Compared with I/R group, the percentage of the area of myocardial infarction was significantly decreased in RIPC group and RIPC-EXO+ I/R group, the serum cTnI concentration and Bax/Bcl-2 ratio in myocardial tissues were significantly decreased in RIPC-EXO+ I/R group ( P<0.05), and no significant change was found in the percentage of the area of myocardial infarction in RIPC+ P group ( P>0.05). The percentage of the area of myocardial infarction was significantly larger in RIPC+ P group than in RIPC group ( P<0.05). Compared with RIPC-EXO+ I/R group, the percentage of the area of myocardial infarction was significantly increased, and the serum cTnI concentration and Bax/Bcl-2 ratio were increased in RIPC+ P-EXO+ I/R group ( P<0.05). Cell experiment Compared with C group, the cell viability was significantly decreased, and the Bax/Bcl-2 ratio was increased in H/R group ( P<0.05). Compared with H/R group, the cell viability was significantly increased, and the Bax/Bcl-2 ratio was decreased in RIPC-EXOc group ( P<0.05). Compared with RIPC+ EXOc group, the cell viability was significantly decreased, and the Bax/Bcl-2 ratio was increased in RIPC+ P-EXOc group ( P<0.05). Conclusions:Propofol may abolish the myocardial protective effect of RIPC by decreasing the production and release of serum exosomes in rats.
