ABSTRACT
Objective: To investigate the inhibitory effect of leonurine on cardiomyocyte hypertrophy induced by angiotensin Ⅱ(Ang Ⅱ) and its effect on p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and miRNA-1.Method: Cardiomyocyte hypertrophy was induced by Ang Ⅱ (0.1 μmol·L-1) in primary neonatal cardiomyocytes. Experiments were designed in 6 groups as following:normal group, model group, p38 MAPK inhibitor group (SB203580, 10 μmol·L-1), low-dose(5 μmol·L-1), middle-dose(10 μmol·L-1) and high-dose(20 μmol·L-1) group. The cardiomyocyte surface area was measured by image software, and the protein contents were detected by Lowry. The concentrations of ANP in the culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The expression level of miRNA-1 was detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the protein expression levels of endothelin-1 (ET-1), p38 MAPK, p-p38 MAPK, myocyte enhancer factor 2 (MEF2), β-myosin heavy chain (β-MHC), α-myosin heavy chain (α-MHC) were detected by Western blot.Result: Compared with normal group, the surface area of cardiomyocyte, the protein contents, the concentrations of ANP, and the protein expression levels of ET-1, p38 MAPK, p-p38 MAPK, MEF2, β-MHC in model group were higher (Pα-MHC and miRNA-1 were lower than those in normal group (Pβ-MHC in high-dose group were lower (Pα-MHC and miRNA-1 were higher than those in model group (PConclusion: Leonurine (20 μmol·L-1) could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and the mechanism is related to the inhibition of activation of p38 MAPK signaling pathway and up-regulation the expression of miRNA-1.
ABSTRACT
<p><b>BACKGROUND</b>A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.</p><p><b>METHODS</b>Adult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.</p><p><b>RESULTS</b>Changes of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.</p><p><b>CONCLUSIONS</b>The domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.</p>