Therapeutic potential of exosome derived from remote ischemic conditioning in alleviating neurologic dysfunction after cardiac arrest in a rat model
10.3760/cma.j.issn.1671-0282.2024.07.018
- VernacularTitle:远端缺血适应外泌体对大鼠心脏骤停后脑损伤的保护作用
- Author:
Heng ZHAI
1
;
Jihui WANG
;
Xi CHEN
;
Yang ZHANG
;
Shuqun HU
;
Jun WANG
;
Yigen PENG
;
Ningjun ZHAO
;
Xianliang YAN
;
Chenglei SU
;
Tie XU
Author Information
1. 徐州医科大学附属医院急诊医学科，徐州 221006
- Keywords:
Remote ischemic conditioning;
Exosomes;
Cardiac arrest;
Neuroprotection;
Glycocalyx;
Hyaluronic acid;
Syndecan-1;
Matrix metalloproteinase 2;
Matrix metallopr
- From:
Chinese Journal of Emergency Medicine
2024;33(7):991-998
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the therapeutic effect of exosomes derived from remote ischemic conditioning on neurological dysfunction after cardiopulmonary resuscitation in a rat model of cardiac arrest and the relationship with glycocalyx protection.Methods:Exosomes were isolated from the blood of healthy adult male Sprague-Dawley rats using ultracentrifugation after undergoing remote ischemic conditioning for use as intervention drugs. Nanoparticle tracking analysis technology was used for exosome detection. Thirty-six adult male Sprague-Dawley rats were randomly assigned to 3 groups ( n=12 each) :Sham group, Control group and Exosome group. Cardiac arrest was induced by asphyxia for 7 min in the Control and Exosome groups. Placebo or exosomes (1×10 10 Particles) were infused intravenously at 5 min after the rats had returned of spontaneous circulation. Neuropsychological deficit score (NDS), open field test, Y maze and Morris water maze were used to assess neurological outcomes. The levels of plasma Hyaluronic acid (HA) and syndecan-1 (Sdc-1) were detected by Elisa. The expression levels of matrix metalloproteinase-2/9 (MMP-2/9) in hippocampal CA1 region were detected by Western blot. Results:After undergoing remote ischemic conditioning, the plasma levels of exosomes were elevated in rats compared to normal rats. Compared with the control group, the behavioral experiment of rats in the exosomes group were significantly improved, as evidenced by an increase in horizontal locomotor distance (5.86±2.89 vs. 17.53±5.51, P< 0.05), an increase in the correct rate of spontaneous alternation (13.29±15.07 vs. 42.63±10.25, P< 0.05), and a shortening of avoidance latency (25.83±8.54 vs. 13.49±4.55, P< 0.05). Plasma HA and Sdc-1 levels were significantly lower 24 h after resuscitation (HA: 26.34±9.83 vs. 14.84±6.26, P< 0.05; Sdc-1: 0.05±0.03 vs. 0.02±0.02, P<0.05), along with significantly lower MMP-2/9 levels in hippocampal tissue. Conclusions:Exosomes extracted from the plasma of rats undergoing remote ischemic conditioning can improve neurological dysfunction after cardiac arrest in rats, and the mechanism may be related to the inhibition of metalloproteinases and the reduction of endothelial glycocalyx degradation.
