ABSTRACT
Right ventricular (RV) dysfunction and failure contribute to the increasing morbidity and mortality of cardiovascular diseases; however, current treatment strategies are grossly inadequate. Sheng-Mai-San (SMS) has been used to treat heart diseases for hundreds of years in China, and its protective effects on RV have not been observed. The present study was to investigate the protective effects of SMS aqueous extract on RV dysfunction in chronic intermittent hypoxia (CIH) mice model. The results showed that CIH mice model presented RV dysfunction and maladaptive compensation after 28-day-CIH and SMS treatment significantly reversed these changes. Diastolic function of RV was restored and systolic dysfunction was attenuated, including elevation of RV stroke volume and fractional shortening, as well as pulmonary circulation. Structurally, SMS treatment inhibited RV dilation, cardiomyocytes vacuolization, ultrastructure abnormalities, and the expression of cleaved caspase-3. Of importance, SMS showed remarkable antioxidant activity by decreasing the levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), increasing the levels of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1), as well as inhibiting the overexpression of 3-NT in RV. Our results indicate that SMS preserve RV structure and function in CIH-exposed mice by involving regulation in both ROS and Reactive Nitrogen Species (RNS) production.
ABSTRACT
Sheng-Mai-San (SMS), a well-known Chinese medicinal plant formula, is widely used for the treatment of cardiac diseases characterized by deficiency of Qi and Yin syndrome. A mouse chronic intermittent hypoxia (CIH) model was established to mimic the primary clinical features of deficiency of Qi and Yin syndrome. Mice experienced CIH for 28 days (nadir 7% to peak 8% oxygen, 20 min per day), resulting in left ventricle (LV) dysfunction and structure abnormalities. After administration of SMS (0.55, 1.1, and 5.5 g·kg(-1)·d(-1)) for four weeks, improved cardiac function was observed, as indicated by the increase in the ejection fraction from the LV on echocardiography. SMS also preserved the structural integrity of the LV against eccentric hypotrophy, tissue vacuolization, and mitochondrial injury as measured by histology, electron microscopy, and ultrasound assessments. Mechanistically, the antioxidant effects of SMS were demonstrated; SMS was able to suppress mitochondrial apoptosis as indicated by the reduction of several pro-apoptotic factors (Bax, cytochrome c, and cleaved caspase-3) and up-regulation of the anti-apoptosis factor Bcl-2. In conclusion, these results demonstrate that SMS treatment can protect the structure and function of the LV and that the protective effects of this formula are associated with the regulation of the mitochondrial apoptosis pathway.
Subject(s)
Cardiomyopathies/drug therapy , Drugs, Chinese Herbal/therapeutic use , Heart Ventricles/drug effects , Myocardium/pathology , Oxygen/metabolism , Phytotherapy , Ventricular Dysfunction, Left/drug therapy , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Apoptosis , Cardiomyopathies/etiology , Caspase 3/metabolism , Cytochromes c/metabolism , Disease Models, Animal , Drug Combinations , Drugs, Chinese Herbal/pharmacology , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Hypoxia , Male , Mice, Inbred ICR , Mitochondria/drug effects , Mitochondria/metabolism , Qi , Up-Regulation , Ventricular Dysfunction, Left/etiology , bcl-2-Associated X Protein/metabolismABSTRACT
Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of rice bacterial leaf blight, one of the most important rice bacterial diseases in China and many other countries. The upstream portions of 41 candidate genes encoding non-transcription activator-like effectors of Xoo Chinese strain 13751 were fused with the coding sequence of AvrBs159-445 in a broad host-range vector. The constructed plasmids were respectively introduced into Xoo strain 13751 and avrBs1 deletion mutant of X. campestris pv. campestris strain 8004 by tri-parental conjugation. The resultant transconjugants were respectively tested for hypersensitive response (HR) elicitation on pepper ECW-10R. Nine strains were able to elicit HR on pepper, indicating that the nine genes (XOO0037, XOO0103, XOO0110, XOO0315, XOO1488, XOO2875, XOO3150, XOO3222 and XOO4134) encoded effectors. Among them, xopAE 13751 (XOO0110), expressed in Xoo strain 13751 growing in rice leaves, was a new experimentally confirmed effector gene. XopAE13751 contains 11 leucine rich repeats. Furthermore, mutants for the nine effector genes were created in Xoo strain 13751 and subsequently tested for virulence in rice. As a result, only the xopR 13751 (XOO4134) deletion mutant GXMxopR showed a significant reduction in virulence in hybrid rice cv. Teyou63 compared to the wild type. However, the growth of GXMxopR in host plant rice was not affected. These results indicated that xopR 13751 was required for full virulence of Xoo strain 13751 by inducing rice disease tolerance.
