ABSTRACT
AIM: To investigate the effects of puerarin (Pue), an isoflavone derived from Kudzu roots, on angiotensin II (Ang II)-induced hypertrophy of cardiomyocytes in vivo and in vitro. METHODS: C57BL/6J mice were infused with Ang II and treated with Pue (100 mg·kg(-1)·d(-1), po) for 15 d. After the treatment, systolic blood pressure (SBP) and left ventricular wall thickness were assessed. The ratios of heart weight to body weight (HW/BW) and left ventricular weight to body weight (LVW/BW) were determined, and heart morphometry was assessed. Expression of fetal-type genes (ANP, BNP and ß-MHC) in left ventricles was measured using semi-quantitative RT-PCR. Mouse primary cardiomyocytes were treated with Pue (50, 100, 200 µmol/L), then exposed to Ang II (1 µmol/L). ROS level was examined with flow cytometry, the binding activity of NF-κB was determined using EMSA. Western blot was used to measure the levels of ERK1/2, p38 and NF-κB pathway proteins. [(3)H]leucine incorporation was used to measure the rate of protein synthesis. RESULTS: Oral administration of Pue significantly suppressed Ang II-induced increases in the myocyte surface area, HW/BW, LVW/BW, SBP and left ventricular wall thickness. Furthermore, Pue significantly suppressed Ang II-induced increases in ANP, BNP and ß-MHC expression in the left ventricles in vivo. Treatment of cardiomyocytes with Pue (50-500 µmol/L) did not affect the viability of cardiomyocytes in vitro. Pretreatment of cardiomyocytes with Pue dose-dependently inhibited Ang II-induced increases in ROS production, NF-κB binding activity, protein synthesis and cell breadth. Furthermore, pretreatment with Pue significantly suppressed Ang II-induced activation of ERK1/2, p38 and the NF-κB pathway proteins and the expression of ANP and ß-MHC in cardiomyocytes. The positive drug valsartan exerted similar effects on Ang II-induced cardiac hypertrophy in vivo and in vitro. CONCLUSION: Pue attenuates Ang II-induced cardiac hypertrophy by inhibiting activation of the redox-sensitive ERK1/2, p38 and the NF-κB pathways.
Subject(s)
Angiotensin II , Antioxidants/pharmacology , Hypertrophy, Left Ventricular/prevention & control , Isoflavones/pharmacology , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Myocytes, Cardiac/drug effects , NF-kappa B/metabolism , Signal Transduction/drug effects , Ventricular Remodeling/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism , Administration, Oral , Animals , Antioxidants/administration & dosage , Cells, Cultured , Disease Models, Animal , Dose-Response Relationship, Drug , Gene Expression Regulation , Hypertrophy, Left Ventricular/chemically induced , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/enzymology , Hypertrophy, Left Ventricular/genetics , Isoflavones/administration & dosage , Male , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Myocytes, Cardiac/enzymology , Myocytes, Cardiac/pathology , Oxidation-Reduction , Protein Kinase Inhibitors/pharmacology , Reactive Oxygen Species/metabolism , Tetrazoles/pharmacology , Ultrasonography , Valine/analogs & derivatives , Valine/pharmacology , Valsartan , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitorsABSTRACT
The aim of this study was to evaluate the clinical and radiographic results of cementless acetabular revision with deep frozen morsellised allografts. Sixty-one patients (65 hips) underwent acetabular revision using cementless components and deep frozen morsellised allografts. Fifty-seven hips (53 patients) were reviewed at a mean of 105.1 months (range 72-180 months) after revision. The study group included 29 males and 24 females with a mean age of 46.4 years. One cup underwent further revision for aseptic loosening and two were defined as radiographic failures. The mean time for allograft incorporation was 12.5 months (range 6-24 months) after index surgery. The mean Harris hip score of the patients improved from 61.1 points preoperatively to 91.6 points postoperatively. Linear and cavitary osteolysis was observed in two and 12 hips, respectively. The acetabular revision using cementless components with deep frozen morsellized allografts provides favourable clinical and radiographic results, although the initial disease and age may adversely affect the outcomes.
