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Enormous evidences in clinic and experimental studies have demonstrated that salvianolate (Sal) could treat cardiovascular diseases such as myocardial infarction (MI), but the underlying mechanism was still needed to be explored. This study aims to investigate the effect of Sal on cardiomyocyte remodeling after MI in rats and explore whether the possible mechanism was related to decreasing the β-myosin heavy chain (β-MHC) expression in cardiomyocytes via the calcineurin (CaN)/nuclear factor C3 of the activated T cell (NFATc3) pathway. Both MI model and angiotensin II induced primary myocardial cells obtained from rats were used in this study. After treatment with Sal, the cardiac function was assessed by color Doppler echocardiography, while MI area, myocardial cell area and heart mass index (HMI) were analyzed via Masson and hematoxylin and eosin staining (HE) stain, respectively. Additionally, CaN activity, and CaN, NFATc3, β-MHC mRNA and protein expressions in myocardial tissue and myocardial cells were tested via corresponding methods, mainly including real-time fluorescence-based quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), immunohistochemistry and fluorescence staining analysis. As a result we obtained the high dose of Sal in vivo could perform beneficial effects on cardiomyocyte remodeling of MI rats, mainly manifesting as improving fractional shortening and ejection fraction rates, reducing the MI area, myocardial cross-sectional area and HMI (P<0.05, 0.01), inhibiting the activity of CaN in myocardial tissue, down-regulating β-MHC mRNA and protein expressions, and decreasing the nuclear translocation of NFATc3 (P<0.05). In the in vitro experiments, 10 µmol/L of Sal could inhibit the increase of the myocardial cell area and CaN activity, down-regulate the mRNA and protein of CaN A subunit, β-MHC; and inhibit the nuclear translocation of NFATc3 (P<0.05, 0.01). In conclusion: use of Sal can improve cardiomyocyte remodeling and down-regulate the expression of β-MHC in cardiomyocytes, of which the mechanism might be related to the reduction of the nuclear translocation of NFATc3 as well as the down-regulation of CaNA subunit expression and/or the inhibition of CaN activity. The results will provide a laboratory basis for the clinical application of Sal.
Surficial sediments and water (27 samples each) were collected from three representative lakes collapsed by mining activities in Huaibei, China. Contents of heavy metals (Sb, As, Cd, Pb, Zn) in both water and sediments were detected via atomic absorption spectrophotometry and atomic fluorescence spectrometry, respectively. The variation coefficient (C.V.) of each heavy metal as well as the partition coefficient (Kd) between surficial sediments and water was calculated. The ecological risks of heavy metals in collapsed lakes were assessed via geoaccumulation index (I geo), and we estimated the Pearson correlation coefficients between heavy metals. Together with the real situations around collapsed lakes, we resolved the sources of heavy metals. We found that the contents of heavy metals in water were basically below Surface Water Quality Standard I. The contents of heavy metals in the majority of sediment samples exceeded the background levels in the Yangtze River and Huai River areas, but were below the threshold effect concentration. The spatial distributions of heavy metals in surficial sediments were not uniform, as the C.V.s indicate medium variations. Analysis of Partition coefficient showed that Lieshan collapsed lake (LSH) was under severe risk. An analysis of I geo revealed gentle-medium ecological risks from Sb, As, and Cd. The classification and frequency distributions of I geo of five heavy metals indicate that the ecological risk of Cd was the largest. The ecological risk was lowest in Yangzhuang collapsed lake (YZH). These results were confirmed by analysis of C.V. and Kd. Analysis of heavy metal sources showed that the inputs of Sb and As into the three collapsed lakes were human-driven and very complex, probably due to point-source pollution, including leaching from gangue piles and industrial discharge. Cd mainly originated from non-point-source agricultural pollution, while Pb and Zn might mainly originate from natural sources.
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