ABSTRACT
<p><b>OBJECTIVE</b>To assess the impact of transfection with recombinant adenovirus vector-mediated Klotho gene on myocardial remodeling in a rat model of heart failure (HF) by intraperitoneal injection of isoproterenol.</p><p><b>METHODS</b>Rats were divided into 5 groups by table of exponential random numbers: normal control group, HF group, saline-control HF group, recombinant adenovirus vector transfection group (Ad.EGFP group, 2 × 10¹⁰ pfu, 0.5 ml/rat), pDC316-CMV-EGFP-rKlotho transfection group (Ad.Klotho group, n=5 each). Left ventricular ejection fraction (LVEF) was obtained by echocardiography, hemodynamic parameters obtained by multi-channel physiological recorder, myocardial tissue underwent pathohistological examination. Additionally, the green fluorescin expression was observed on frozen heart section. Myocardial fibrosis correlated gene expression including Klotho gene, collagen I and III was detected by real time-PCR. Moreover, plasma levels of B-type natriuretic peptide (BNP) were measured with ELISA.</p><p><b>RESULTS</b>Compared to saline control HF group, LVEF, LVSP and ±dp/dtmax were significantly increased, myocardial fibrosis and myocardial remodeling were significantly attenuated in the Ad. Klotho group and there was green fluorescin distribution in myocardial tissues of Ad. Klotho group. Klotho expression was down-regulated and collagen I and III expression was upregulated in HF rats compared to normal control group (all P<0.05) and these changes could be significantly reversed in Ad. Klotho group (all P<0.05). Plasma BNP level was also significantly lower in Ad. Klotho group than in HF group (P<0.05).</p><p><b>CONCLUSIONS</b>Klotho gene transfection could improve cardiac function and attenuate cardiac remodeling and reducing myocardial fibrosis.</p>
Subject(s)
Animals , Rats , Adenoviridae , Disease Models, Animal , Echocardiography , Gene Expression , Genetic Vectors , Glucuronidase , Heart Failure , Hemodynamics , Isoproterenol , Myocardium , Natriuretic Peptide, Brain , Transfection , Ventricular Function, LeftABSTRACT
Objective To investigate the effects of antithyroid drug(ATD) on oxidative stress in Graves disease patients with and without infiltrative ophthalmopathy.Method The levels of superoxide dismutase(SOD),glutathione peroxidase(GPx) and catalase(CAT) in erythrocytes of Graves disease patients(18 with and 20 without infiltrative ophthalmopathy) were measured before and after treatment with ATD.Results Compared with the normal control group,the levels of SOD,GPx and CAT were significantly higher in Graves disease patients with and without infiltrative ophthalmopathy.After euthyroidism was achieved with the treatment of ATD,the levels of SOD,GPx and CAT were normalized in the patients without infiltrative ophthalmopathy,but oxidative stress was still present in the patients with infiltrative ophthalmopathy.Conclusion The oxidative stress is obvious in patients with Graves ophthalmopathy,which suggests that oxidative stress is involved in orbital inflammation.
ABSTRACT
Objective To investigate the toxic effect of immunosuppressive drugs on apoptosis of rat pancreatic islet cells in vitro and the protective action of Bcl-2.Methods Islet cells expressing Bcl-2 and the control islet cells were cultured at different concentrations of tacrolimus and the apoptosis rate of islet cells and insulin accumulation in the culture medium were detected after 48h.Results Low and high concentrations of tacrolimus induced the apoptosis of islet cells and decreased insulin secretion.The Bcl-2 inhibited the apoptosis of islet cells induced by tacrolimus and improved the insulin secretion.Conclusion Tacrolimus may directly damage to isolated rat islet cells and the expression of Bcl-2 can protect the cells from the damage of immunosuppressive drugs.