ABSTRACT
Chronic heart failure (CHF) is one of the most common chronic diseases with increasing incidence and mortality. Liquiritigenin (LQG) is shown to protect mice from cardiotoxicity. However, its underlying mechanism remains unclear. Our study aimed to reveal the role of ARHGAP18 in LQG-mediated cardioprotective effects in CHF. In the current study, CHF cell model and rat model were established by the application of doxorubicin (DOX). The reactive oxygen species (ROS) level and cell apoptosis were determined by flow cytometry. The cardiac function of rats was evaluated by measuring left ventricular systolic pressure, left ventricular end diastolic pressure, and serum level of lactate dehydrogenase and brain natriuretic peptide. The expression of active RhoA was elevated and that of ARHGAP18 was decreased in DOX-induced CHF cell model. ARHGAP18 could reduce DOX-induced RhoA activation, ROS elevation, and cell apoptosis. Meanwhile, the knockdown of ARHGAP18 could promote the activation of RhoA, the level of ROS, and the rate of cell apoptosis, which could be reversed by the application of RhoA inhibitor. LQG promoted the expression of ARHGAP18 and exerted similar effects of ARHGAP18 in CHF cell model. The application of LQG could also reverse the effects mediated by ARHGAP18 knockdown. Moreover, LQG significantly improved cardiac function and ameliorated DOX-induced cardiotoxicity of CHF rats. In conclusion, LQG could alleviate DOX-induced CHF via promoting ARHGAP18 and suppressing RhoA/ROCK1 pathway. LQG was a potential agent for CHF treatment.
Subject(s)
Flavanones/pharmacology , GTPase-Activating Proteins/metabolism , Heart Failure/drug therapy , rho GTP-Binding Proteins/antagonists & inhibitors , rho-Associated Kinases/antagonists & inhibitors , Animals , Apoptosis/drug effects , Cell Line , Chronic Disease , Disease Models, Animal , Down-Regulation , Doxorubicin/toxicity , GTPase-Activating Proteins/antagonists & inhibitors , GTPase-Activating Proteins/genetics , Gene Knockdown Techniques , Glycyrrhiza/chemistry , Heart Failure/chemically induced , Heart Failure/metabolism , Medicine, Chinese Traditional , Plants, Medicinal , Rats , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , rho GTP-Binding Proteins/metabolism , rho-Associated Kinases/metabolismABSTRACT
OBJECTIVE: To evaluate the clinical effect of Xuefu Zhuyu Decoction (XFZYD) on the incidence of complications of rib fracture in patients with blunt chest injury. METHODS: One hundred and twenty patients with rib fracture stratified according to the AIS scale in three layers (1-3) were equally assigned to two groups, the treated group and the control group, all received conventional treatment, but XFZYD was administered to patients in the treated group additionally. The incidence of complications in patients, including atelectasis, pleural effusion, pulmonary contusion, pleurocentesis and closed thoracic drainage, were observed. RESULTS: The incidence of pleural effusion in patients of AIS-1 and -2 in the treated group was 20% and 45% respectively, which was remarkable lower than that in the control group (55% and 85%) respectively (P < 0.05); in the treated group, 10% patients of AIS-3, for whom close thoracic drainage was applied, while in the control group, the percentage reached 60%, showing significant difference between groups (P < 0.05). CONCLUSION: XFZYD could reduce the incidence of pleural effusion in patients with blunt chest injured rib fracture of AIS-1 or -2, and reduce the utilization of close thoracic drainage in those of AIS-3, so it is good for clinical practice.