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Objective:To investigate the regulatory effect of miR-26a in radiation-induced heart disease (RIHD) mice.Methods:C57/BL6 mice were used to establish RIHD models. The cardiac function, fibrosis, the expression levels of collagen 1 (COL1) and connective tissue growth factor (CTGF), and miR-26a were detected in RIHD mice. Whether CTGF was the target gene of miR-26a was verified by dual luciferase kit. Moreover, cardiac fibroblasts were transfected with miR-26a up and miR-26a down lentivirus vectors to construct the miR-26a overexpression and underexpression cell models. The expression of CTGF, proliferation, and apoptosis of cardiac fibroblasts were detected.Results:In the RIHD mice, heart function was decreased, myocardial fibrosis was remodeled, the expression levels of COL1 and CTGF were up-regulated, and the expression level of miR-26a was down-regulated. Dual luciferase reporter assay confirmed that CTGF was the target gene regulated by miR-26a. Overexpression of miR-26a could inhibit the expression of CTGF, suppress the proliferation of cardiac fibroblasts, promote cell apoptosis and secrete collagen. Underexpression of miR-26a yielded the opposite results.Conclusion:MiR-26a affects the function of cardiac fibroblasts by targeting CTGF and probably mediates the process of radiation-induced myocardial fibrosis, which may become a new regulatory target of RIHD.
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Objective:To investigate the regulatory role of microRNA in radiation-induced heart disease (RIHD) in mice and provide a new strategy for its treatment.Methods:Based on the Gene Expression Omnibus database (GSE147241), which includes normal heart tissue and irradiation heart tissue, we conducted bioinformatics research and analysis to determine the differentially-expressed genes. Then, thirty male C57/BL6 mice were randomly divided into the control group, irradiation group and miR-133a overexpression intervention group. The heart received single dose of X-ray 20 Gy in the irradiation group and miR-133a overexpression intervention group, but not in the control group, and then fed for 16 weeks. Cardiac function was assessed by echocardiography. Myocardial fibrosis was detected by Masson staining. The expression levels of miR-133a, CTGF, COL-1 and COL-3 mRNA were detected by qRT-PCR. The expression levels of CTGF, COL-1 and COL-3 proteins were detected by western blot.Results:miR-133a was the differentially-expressed gene between the irradiation and control groups. Overexpression of miR-133a could mitigate the decrease in cardiac function and increase in myocardial collagen content ( P<0.01). Meantime, overexpression of miR-133a could down-regulate the expression levels of CTGF, COL-1, COL-3 mRNA and protein ( P<0.01). Conclusions:Radiation increases the synthesis of collagen and leads to myocardial fibrosis remodeling. Overexpression of miR-133a can alleviate the radiation-induced myocardial fibrosis.
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Objective:To establish the C57BL/6 mouse models of radiation-induced cardiopulmonary dysfunction.Methods:Twenty-four male C57BL/6 mice were randomly divided into the control and irradiation groups. Mice in the irradiation group were irradiated with 20 Gy electron beam and bred for 6 months after irradiation. Cardiac function was assessed using ultrasonography. The partial pressure of oxygen was detected by blood gas analysis. Cell apoptosis was observed by Tunel assay. Myocardial and pulmonary fibrosis was assessed by Masson staining.Results:The LVEF in the irradiation group was (68.60±10.92)%, significantly less compared with (81.75±8.79)% in the control group ( P< 0.01). The apoptotic index of heart in the irraiation group was (23.90±6.60)%, considerably higher than (3.25±3.38)% in the control group ( P< 0.01). The CVF of heart in the irradiation group was (15.42±5.72)%, significantly higher than (1.45±0.64)% in the control group ( P< 0.01). The PaO 2 level in the irradiation group was (86.10±7.60) mmHg, significantly lower compared with (107.16±9.01) mmHg in the control group ( P< 0.01). The apoptotic index of lung in the irradiation group was (27.90±8.94)%, significantly higher than (2.50±3.55)% in the control group ( P<0.01). The CVF of lung in the irradiation group was (17.76±5.77)%, remarkably higher than (2.50±3.55)% in the control group ( P< 0.01). Conclusion:Radiation can induce cardiopulmonary apotosis and fibrosis remodeling, which leads to cardiopulmonary dysfunction, suggesting the successful establishment of C57BL/6 mouse model of radiation-induced cardiopulmonary dysfunction.
