Discussion about the Role of Ghrelin in Myocardial Ischemia/Reperfusion and its Possible Mechanism
Authors: Huang Gang , Zheng Nan , Huang Yinqing 
Published: October 2024

Background

Ghrelin in the gastric mucosa of rats can improve myocardial cell apoptosis and cardiac remodeling during myocardial ischemia and myocardial infarction, and it has a protective effect on the myocardium, but its mechanism is unclear.

Objectives

The rat myocardial ischemia/reperfusion (I/R) model was established to investigate Ghrelin’s role in the disease’s pathogenesis.

Materials and Methods

The study subjects were 80 male and female Sprague-Dawley (SD) rats: Sham operation group, I/R model control group, I/R + Ghrelin group, and I/R + Ghrelin + 5-hydroxydecanoic acid salt (5-HD) group. Before surgery, rats in the I/R + Ghrelin group were given Ghrelin 100 µg/kg intravenously, and those in the I/R + Ghrelin + 5-HD group were given 100 µg/kg and 5-HD 5 mg/kg. An I/R model was made, and a cardiac ultrasound index was detected after reperfusion. The venous blood of rats in each group was taken, with the values of the myocardial enzyme creatine kinase (CK), troponin I (cTnI), and so on. Malondialdehyde (MDA) and adenosine triphosphate (ATP) were measured from the myocardial tissues of rats. Mitochondrial protein was extracted from the ischemic myocardium cells of rats in each group, and the content of Cx43 protein in the mitochondria was detected.

Results

After reperfusion, it was found that left ventricular developed pressure (LVDP), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) in the echocardiogram of the I/R model control group were significantly decreased, and the difference was statistically significant compared with the sham operation group (p < .001). LVDP, LVEF, and LVFS in the I/R + Ghrelin group were significantly higher than those in the I/R model control group, and the difference was statistically significant (p < .001). At the end of reperfusion, myocardial troponin and other data, as well as MDA content in the peripheral blood of the control group, were different from those in the sham operation group (p < .05). The former ATP value was lower than the latter (p < .05). The CK, CK-myocardial band (CK-MB), and cTnI values in the I/R + Ghrelin group were lower than those in the good group (p < .05). Mitochondria were isolated from rat myocardial cells in each group. After reperfusion, Cx43 data in the control group were lower than those in other groups. After pretreatment with Ghrelin, related expressions were unchanged. After 5-HD was added, the expression of Cx43 decreased slightly, but it was not obvious. The content of MDA in the I/R + Ghrelin + GHRP-6 group was significantly increased, which was not significantly different from that in the I/R + Ghrelin + 5-HD group. Still, the expression was reversed considerably compared with that in the I/R + Ghrelin group, and the difference was statistically significant (p < .001). After the intervention of GHRP-6, ATP content in the myocardial tissue of rats in the I/R + Ghrelin group was also reversed, and the difference was statistically significant (p < .05). By western blot detection, it was found that after the intervention of GHRP-6 in the rats pretreated with Ghrelin, the expression level of Cx43 in the myocardial mitochondria of the rats was significantly decreased. Still, the difference was insignificant compared to that in the I/R + Ghrelin + 5-HD group. Ghrelin protein reduces the mitochondrial ATP value, and reperfusion can maintain the stability of energy metabolism of myocardial cells and protect them. Ghrelin protein protects the myocardium by maintaining the expression of Cx43. Ghrelin protein can maintain the expression of Cx43 by increasing the activity of the mitochondrial ATP-sensitive potassium channel, thus playing a protective role in cardiomyocytes to a certain extent.