Abstract
Background Radiation-induced heart damage is considered to be a progressive process of fibrosis. Emerging evidence has indicated that the Smads and matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs (TIMP) may be involved in radiation-induced cardiac fibrosis (RICF) by regulating the activation of TGF-β1 signaling pathway. Based on this, the present study was undertaken to characterize the effect of Huangqi Shengmai Yin (HSY) on RICF in a rat model. Methods Precardiac region of rats was irradiated with 25 Gy X-rays, and their myocardial pathology scores in terms of injury and collagen volume fraction (CVF) and the expression levels of fibrotic molecules were detected. Results The pathology scores and CVF in myocardial tissue increased after irradiation, and the expression of TGF-β1, Col1, and Col3 increased. This change indicated that such irradiation promoted the fibrosis damage in rat hearts. The damage was accompanied by an increase in the expression of Smad 2, Smad3, Smad4, and MMP14 and a decrease in the expression of Smad 7 and TIMP1. Administration of HSY weakened the RICF by decreasing pathology score and CVF and decreased the expression of TGF-β1, Col1, and Col3 in irradiated rat hearts. In addition, Smad2, Smad3, Smad4, and MMP14 were downregulated, while Smad 7 and TIMP1 were upregulated during intervention with HSY. Conclusions The involvement of the TGF-β1/Smads and MMPs/TIMP system in RICF was confirmed. This study demonstrated, for the first time, that HSY attenuates the effects of RICF in a rat model. The effect HSY was found to be closely related to the TGF-β1/Smads signaling pathway and MMPs system. These results suggest that HSY is a prospective drug for clinical treatment of RICF.
Highlights
Radiotherapy treatment for thoracic and abdominal tumors can affect the heart which locates in the mediastinum and cause radiation-induced heart damage (RIHD) [1]
Our study indicated that the myocardial pathology injury score in the control group (Con) group was the lowest (
The results showed that fibrosis factors Col1 and Col3 were expressed in cytoplasm and that TGF-β1 is mainly expressed in the cytoplasm and partially expressed in the nucleus (Figure 3)
Summary
Radiotherapy treatment for thoracic and abdominal tumors can affect the heart which locates in the mediastinum and cause radiation-induced heart damage (RIHD) [1]. Shengmai Yin is composed of ginseng, liriope, and Schisandra chinensis and is mainly used for the treatment of coronary heart disease with deficiencies of both Qi and Yin. Chinese astragalus is a holy medicine for nourishing Qi. previous studies have found that astragalus can regulate the expression of fibrosis-related molecule in irradiated cardiac fibroblasts (CFs) [7]. In this study, based on the TGF-β1/Smads and MMPs, we explored the effects and mechanisms of Huangqi Shengmai Yin (adding astragalus to the prescription of Shengmai Yin to form the Huangqi Shengmai Yin decoction, HSY) on a RICF rat model This experimentation provided an evidence-base for the clinical use of HSY to treat RIHD. Emerging evidence has indicated that the Smads and matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs (TIMP) may be involved in radiation-induced cardiac fibrosis (RICF) by regulating the activation of TGF-β1 signaling pathway. These results suggest that HSY is a prospective drug for clinical treatment of RICF
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