ABSTRACT
Aim To investigate whether Linggui Zhugan Decoction ( LGZGD) can inhibit ventricular remodeling and prevent heart failure in rats after myocardial infarction by regulating Nrf2/BNIP3 pathway. Methods The model of heart failure after myocardial infarction was established by left coronary artery ligation in rats. Two weeks after modeling, all rats were randomly divided into model group, LGZGD group, and captopril group. Meanwhile sham operation group was set up. The rats were given continuous intragastric administration with drug or distilled water for 28 days, once a day. The behavioral signs of rats in each group were observed. The cardiac function of rats in each group was examined by echocardiography. Serum BNP and NT-ProBNP content were detected by enzyme -linked immunoassay; The changes of myocardial his-topathological and collagen fibers in rats were detected using sirius staining. The contents of oxidative stress index including ROS, SOD in myocardial tissue of rats in each group were observed by DCFH-DA fluorescent probe and Enzyme-linked immunoassay. The ultra-structure of mitochondria was observed by transmission electron microscopy. Expressions of apoptotic proteins ( mitochondrial CytC, cytoplasmic CytC) were detected by Western blot. Expression of proteins related to the Nrf2/BNIP3 pathway were examined by immunofluorescence and Western blot. Results LGZGD could significantly improve the cardiac function of rats, reduce the contents of BNP and NT-ProBNP, inhibit the excessive deposition of collagen in myocardial interstiti-um, reduce ROS, increase the content of SOD, improve mitochondrial structure damage, up-regulate the expression of Nrf2 and nuclear translocation, and reduce the expression of BNIP3. Conclusions LGZGD can inhibit the ventricular remodeling and prevent the occurrence of heart failure after myocardial infarction. Its pharmacological effects are mainly related to regulating the Nrf2/BNIP3 pathway, activating Nrf2, promoting its nuclear transfer, and further down-regulating BNIP3, protecting mitochondrial function, and reducing cardiomyocyte apoptosis.
ABSTRACT
Cardiovascular disease is the leading cause of death in China. Due to its great individual differences in genetic background, pathogenesis and disease development trend, the survival risk rate after standardized western medicine treatment under the guidance of the current guidelines remains high. Traditional Chinese medicine(TCM) has unique multiple-target, multiple-pathway and multiple-layer advantages, which can effectively make up for shortcomings of western medicine. Therefore, it has been widely used in the treatment of cardiovascular diseases. Oxidative stress is one of the important causes of cardiovascular diseases. Nuclear factor erythroid-2-related factor 2(Nrf2) is the central regulator of this reaction. When being activated, it can transfer to the nucleus and initiate signaling in the downstream pathway, thus playing an anti-oxidative stress role. As one of the most important endogenous protection systems in the body, the Nrf2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway is the most classical approach for Nrf2 in playing roles. There have been certain achievements in studying and clarifying TCM by regulating this pathway to treat cardiovascular diseases using modern molecular biology and other methods. Based on this, this paper summarized the relationship between Nrf2/HO-1 signaling pathway and cardiovascular diseases, then concluded and analyzed the mechanism and pharmacological effects of TCM and its active ingredients in Nrf2/HO-1 signaling pathway on different cardiovascular diseases, involving active ingredients of TCM, TCM pairs active ingredients, TCM extracts and TCM formula. This paper provides a theoretical reference for the development and utilization of anti-cardiovascular drugs.