[Mechanism of Tongguan Capsules in intervention in heart failure based on transcriptomics and experimental...

This study aimed to investigate the effects of Tongguan Capsules(TG) on isoproterenol(ISO)-induced heart failure(HF) in rats, and to comprehensively predict the potential molecular mechanisms underlying TG's effects in improving HF based on transcriptomic analysis. Additionally, the study explored the mechanisms by which TG intervenes in extracellular matrix(ECM) remodeling to prevent and treat myocardial fibrosis and HF. A rat model of HF was established by subcutaneous injection of ISO(10 mg·kg~(-1)), and the rats were randomly divided into four groups: control group, model group, captopril group, and TG group. Cardiac function was assessed using echocardiography after 14 days of modeling and treatment. Biochemical markers including lactate dehydrogenase(LDH), malondialdehyde(MDA), and superoxide dismutase(SOD) were measured. Myocardial fibrosis was assessed using hematoxylin-eosin(HE), Masson's trichrome, and Sirius red staining. Transcriptomic analysis was performed to screen and analyze differentially expressed genes among the control, model, and TG groups, to predict key targets and pathways involved in TG's preventive and therapeutic effects against HF. In addition, quantitative real-time polymerase chain reaction(qPCR) and Western blot were used to detect the effects of TG on the mRNA and protein expression levels of collagen type Ⅰ(ColⅠ), collagen type Ⅲ(Col Ⅲ), matrix metalloproteinase 2(MMP2), and fibronectin(FN-1). Compared with the model group, TG treatment for two weeks improved cardiac function in rats with ISO-induced HF. TG significantly reduced cardiac weight index, LDH, and MDA levels, and significantly increased SOD activity(P<0.05). Histopathological results showed that TG alleviated ISO-induced pathological changes in cardiac tissue and reduced collagen accumulation. Transcriptomic analysis suggested that TG may exert cardioprotective effects by regulating the ECM-receptor interaction pathway via key genes such as collagen1a1, collagen3a1, and MMP2. The qPCR and Western blot results further confirmed that TG inhibited the expression of ColⅠ, ColⅢ, MMP2, and FN-1 compared with the model group. In conclusion, TG alleviates myocardial injury caused by ISO-induced HF, improves cardiac function, mitigates pathological morphological and structural changes, and regulates the expression and deposition of ECM proteins in the myocardium of HF rats.