Pathological manifestations of acute-stage radioactive myocardial damage and related mechanisms

Objective: To investigate the pathological manifestations of acute-stage radioactive myocardial damage and related mechanisms using an experimental animal model. Methods: A total of 12 adult male Sprague-Dawley rats were randomly divided into control group and radiation group. In the radiation group, the model of radiation-induced myocardial damage was established by the irradiation of the anterior myocardial territory with 6-MV X-ray at a single dose of 20 Gy, and at 14 days after irradiation, HE staining was used to observe the morphological changes of cardiomyocytes and intercellular matrix, and Masson staining was used to observe the distribution of collagen fibers. The collagen volume fraction (CVF) was used for semi-quantitative analysis. ELISA was used to measure the activity of total superoxide dismutase (T-S0D) and the concentration of malondialdehyde (MDA), and Western blot was used to measure the expression of the fibrosis marker protein collagen type I (C0L-1) and the endoplasmic reticulum stress-related proteins GRP78 and CH0P. The t-test, t'-test, or nonparametric rank sum test was used for comparison between groups. Results: At 14 days after local irradiation of the heart, the radiation group had disordered arrangement of cardiomyocytes, marked edema, rupture of some cardiomyocytes, mild karyopyknosis in cardiomyocytes, and infiltration of inflammatory cells in the myocardial interstitium, compared with the control group. Collagen fibers in the myocardial tissue were mainly distributed in the perivascular area and cardiomyocyte interstitium. The radiation group had a significantly higher CVF than the control group (11.35% vs. 5.23%, P = 0.000) and a significant increase in the expression of C0L-1 compared with the control group (P = 0.000). The radiation group had significant increases in the activity of T-SOD and the concentration of MDA in the myocardial tissue compared with the control group (T-SOD: 156.61 U/mgprot vs. 137.06 U/mgprot, P = 0.042; MDA: 2.36 nmol/mgprot vs. 1.31 U/mgprot, P = 0.007). Compared with the control group, the radiation group showed significant increases in the expression of endoplasmic reticulum stress-related proteins GRP 78 and CHOP (P = 0.037 and 0.009). Conclusions: The pathological manifestations of acute-stage myocardial damage include degeneration of cardiomyocytes, inflammatory exudation in the interstitium, and deposition of collagen in the perivascular area and myocardial interstitium. Myocardial fibrosis can be observed in the acute stage of radiation-induced myocardial damage, and the mechanism may be related to oxidative stress and endoplasmic reticulum stress induced by radioactive rays. (authors)