The mechanism of ultrasound-visualized hydrogen microbubbles in inhibiting inflammatory progression and alleviating myocardial ischemia reperfusion injury in rats
10.3760/cma.j.cn421203-20240115-00011
- VernacularTitle:超声靶向氢气磷脂微泡抑制炎症减轻大鼠心肌缺血再灌注损伤的机制研究
- Author:
Minjie ZHANG
1
;
Xiaoshan ZHANG
;
Ying WEI
;
Qi CHEN
;
Xiongfeng LI
;
Lingfeng MA
;
Yaxi WANG
Author Information
1. 内蒙古医科大学附属医院超声科，呼和浩特 010050
- Publication Type:Journal Article
- Keywords:
Ischemia reperfusion injury;
Myocardial;
Ultrasonic;
Hydrogen;
Phospholipid microbubbles
- From:
Chinese Journal of Organ Transplantation
2025;46(10):723-730
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the mechanism by which hydrogen alleviates myocardial ischemia/reperfusion injury (IRI) through ultrasound-targeted destruction of hydrogen-loaded phospholipid microbubbles in the ischemic myocardium of rats.Methods:A total of 45 rats were randomly divided into three groups: sham operation group, IRI group (model group), and hydrogen treatment group (experimental group), with 15 rats in each group. A rat model of myocardial IRI was established. Rats in the sham group received 0.2 ml of normal saline via the tail vein, those in the model group received 0.2 ml of phospholipid microbubbles without hydrogen, and those in the treatment group received 0.2 ml of hydrogen-loaded phospholipid microbubbles. After 24 hours, cardiac function was assessed by left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Serum levels of cardiac troponin I (cTnI), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Expression levels of Janus knase 2(JAK2), signal transducer and activator of transcription 3(STAT3), phosphorylated JAK2(p-JAK2), and phosphorylated STAT3(p-STAT3) proteins in myocardial tissue were detected by Western blot. Myocardial infarct size was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and myocardial histopathological changes were observed by hematoxylin-eosin (HE) staining.Results:After 24 hours of reperfusion, LVEF [(54.26±2.92) % vs (45.77±27%)] and LVFS [(24.11±1.68) % vs (19.50±1.19%)] were significantly higher in the treatment group than in the model group (both P<0.001). ELISA results showed that levels of CK-MB [(13.58±2.07) μg/L vs (20.07±1.57) μg/L], LDH [(47.76±8.32) μg/L vs (74.39±10.19) μg/L], cTnI [(7.50±0.26) μg/L vs (9.05±0.34) μg/L], and IL-6 [(121.34±8.97) ng/L vs (156.99±6.46) ng/L] were significantly lower in the treatment group compared with the model group (all P<0.001). TTC staining revealed a smaller infarct size in the treatment group [(48.77±2.68)%] than in the model group [(63.53±3.10)%, P<0.001]. Western blot analysis showed that the expression levels of JAK2 and p-STAT3 proteins were significantly lower in the treatment group than in the model group ( P<0.05). HE staining showed no pathological abnormalities in major organs (heart, liver, spleen, lung, and kidney) following hydrogen microbubble treatment. Conclusions:Ultrasound-targeted destruction of hydrogen microbubbles enables local hydrogen release in the myocardium, which downregulates IL-6 and inhibits activation of the JAK/STAT signaling pathway, thereby attenuating inflammation and reducing ischemia/reperfusion injury.
