Effects of thyroid hormones on cardiac function in mice by inducing expression of B-cell activating factor in cardiomyocytes / 医学研究生学报

ABSTRACT

Objective　High levels of triiodothyronine (T3) can lead to hyperthyroid heart disease, but its mechanism is unclear. This study aims to investigate the effects of T3 on the expression of B-cell activating factor (BAFF) in cardiomyocytes and to explore its possible role in the pathogenesis of hyperthyroid heart disease.　Methods　Sixty healthy C57BL/6J mice were selected and randomly divided into two groups the experimental group and the control group. The experimental group received intraperitoneal injection of T3 at 5 μg/ml, one time/d, for 42 consecutive days. The concentrations of serum T3 and tetraiodothyronine (T4) were detected by radioimmunoassay; ELISA was used to determine BAFF expression in peripheral blood, and the cardiac index and the transverse diameter of myocardial cells in each group were determined. Immunohistochemistry and Western blot were used to detect the expression of BAFF protein in myocardium and of myocardial tumor necrosis factor-α (TNF-α) protein; the expression of BAFF mRNA in myocardium was detected by Real-Time PCR; flow cytometry (FCM) was used to detect changes in the proportion of B-cells in the heart.　Results　Compared with the control group, the serum T3 concentration, cardiac index, BAFF and myocardial cell transverse diameter of the experimental group significantly increased (P<0.05), and the T4 concentration decreased (P<0.05). Under the light microscope, the cardiomyocytes of the control group were normal, while those of the experimental group were hypertrophied and disordered in structure. Compared with the control group (0.765±0.164), BAFF protein expression significantly increased in the experimental group (1.865±0.290) (P<0.05). Compared with the control group (0.537±0.089), the expression of TNF-α protein significantly increased in the experimental group (0.737±0.065) (P<0.05). Correlation analysis of T3 with BAFF gene expression in cardiomyocytes and BAFF level in peripheral blood showed that T3 was positively correlated with both the former with a correlation coefficient of 0.637 (P<0.01) and the latter with 0.778 (P<0.01). For FCM, compared with the control group [(12.40±1.09)%], the proportion of myocardial B-cells increased in the experimental group [(16.12±0.631)%] (P<0.05).　Conclusion　High concentration of T3 can promote the expression of BAFF in myocardial cells and lead to the activation of B-cells, thus increasing the inflammatory response and leading to myocardial hypertrophy.