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Objective To explore whether physiological doses of testosterone therapy can modulate cardiomyocyte aging via classical androgen receptor (AR) dependent pathways.Methods Male C57BL/6J mice and testicular feminized (Tfm) mice were divided into five experimental groups:the control group (n=8),the castrated group (n=8),the Tfm group (n=7),the testosterone treated castrated group (n=8),and the testosterone-treated Tfm group (n =8).After isolation of cardiomyocytes from the left ventricle,the activity of superoxide dismutase (SOD) and the amount of malondialdehyde (MDA) were measured using colorimetry,and the expression of the p16INK4a and retinoblastoma (Rb) proteins was detected by Western blotting.Results Compared with the control group,the activity of SOD in the castrated group and the Tfm group declined [(16.55±1.18) U/ml,(17.30±1.32) U/ml vs.(21.57±2.21)U/ml,P＜0.05)],the amount of MDA increased [(7.78±1.27)μmol/L,(6.52±0.82)μmol/L vs.(3.48±0.70)μmol/L],P＜0.01,and the expression of both the p16INK4aand Rb proteins increased [(0.37±0.08),(0.45±0.06) vs.(0.14±0.02),forp16INK4a,P＜0.05; (0.74±0.05),(0.79±0.08) vs.(0.40±0.05),for Rb,P＜0.05].Compared with the castrated group,the activity of SOD in the testosterone treated castrated group increased [(23.00±0.58)U/ml vs.(16.55±1.18) U/ml,P＜0.01],the amount of MDA decreased [(2.63±0.90) μmol/L vs.(7.78±1.27) μmol/L,P＜0.01],and the p16INK4a and Rb proteins were both downregulated (0.13 ± 0.03 vs.0.37± 0.08),for p16INK4a,P＜0.05; (0.45 ±0.05) vs.(0.79±0.08),for Rb P＜0.05.Compared with the Tfm group,the activity of SOD in testosterone-treated Tfm group increased,the amount of MDA decreased,and the p16IN4a and Rb proteins were both downregulated (P＜ 0.05).No significant differences in these markers were detected between the testosterone-treated castrated group and the testosterone-treated Tfm group.Conclusions Physiological doses of testosterone can retard cardiomyocyte aging via androgen receptor independent pathways.
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<p><b>OBJECTIVE</b>To investigate the correlation of the occurrence and prognosis of coronary slow flow phenomenon (CSF) with blood homocysteine (Hcy) levels in patients receiving emergency percutaneous coronary intervention therapy (PCI).</p><p><b>METHODS</b>From January, 2010 to December, 2011, 138 patients with ST-elevation myocardial infarction received emergency angioplasty, among whom 46 patients developed CSF and 92 did not (control group). Blood Hcy levels were determined in these patients. The patients with CSF were classified into two groups with mild and moderate Hcy elevations (32 and 14 cases, respectively), and the left ventricular ejection fraction (LVEF) during hospitalization and at 3 months of follow-up as well as major adverse cardiac events (MACE) were compared between the two groups and analyzed for their association with Hcy level.</p><p><b>RESULTS</b>The patients with CSF showed significantly higher blood Hcy levels than the control patients (P=0.001). At 3 months of follow-up, the patients with CSF and moderate Hcy elevation had significantly lower LVEF (P=0.031) and higher incidence of MACE (P=0.019) than those with mild Hcy elevation. Hcy levels were negatively correlated with LVEF (r=-0.310, P=0.036) and positively with MACE (r=0.342, P=0.02).</p><p><b>CONCLUSION</b>A high blood Hcy level is closely correlated with the occurrence of CSF in emergency PCI, affects the recovery of LVEF and increases the incidence of MACE.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Coronary Artery Disease , Blood , Diagnosis , Therapeutics , Emergency Treatment , Homocysteine , Blood , Percutaneous Coronary Intervention , Prognosis , Stroke Volume , Treatment Outcome , Ventricular Function, LeftABSTRACT
Objective To observe the onset of vascular smooth muscle cell (VSMC) senescence induced by tert-butyl hydroperoxide (t-BHP) and the intervention effect of dehydroepiandrosterone (DHEA). Methods The VSMCs were divided into four groups: blank control group, t-BHP group (incubated with 80 μmol/L t-BHP for 72 h), 10 nmol/L DHEA intervention group (pretreated with 10 nmol/L DHEA 30 min before t-BHP) and 100 nmol/L DHEA intervention group (pretreated with 100nmol/L DHEA 30 min before t-BHP). Two ageing markers of ageing associated β-galactosidase activity and cell proliferation activity were adopted as main indexes. β-galactosidase activity was measured with immunocytochemical method and cell proliferation activity was measured with flowcytometry. Results After continuous treatment with 80 mmol/L t-BHP for 72 h, the ratios of G0/G1 phase cells and SA-β-galactosidase staining positive cells increased as compared with blank controlgroup [(89.4±3.4)% vs. (49.5±5.5)%, (3.5±1.2)% vs. (75.3±4.3)%], which indicated that VSMCs senescence were successfully induced by t-BHP. While the above changes were smaller in 100 nmol/L DHEA intervention group than in t-BHP group. Conclusions With ageing,accumulation of damage produced by reactive oxygen species may be an important mechanism causing the onset of VSMCs senescence. DHEA may be able to retard the progression of VSMCs senescence through antioxidant effect.
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Objective To investigate the effects of ovariectomy and cholesterol rich diet on the change of estrogen receptor content of vascular endothelial cells and hearts of female rats. Methods The receptor binding assay (RBA) was adopted to measure the content of estrogen receptors, and the serum levels of estradiol and lipids were measured. Results The content of ER was much lower in hearts and VEC of ovariectomy〔(0.51?0.09) fmol/mg pro,(6.73 ? 0.52) fmol/106 cell〕and cholesterol rich rats〔(0.97?0.12) fmol/mg pro,(9.15 ?0.53) fmol/106 cell〕than pseudo-operation rats 〔(2.08?0.15) fmol/mg pro ,(17.66?1.26) fmol/106 cell , P
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AIM To observe Arg-Glu*ss activity of antiplatelet and anticoagulation in rats and to further explore its mechanism. METHODS Twenty four male sprague dewley rats were divided into three groups randomly (eight rats in each group).Each group was orally given Arg-Glu (61 4 mg?kg -1 ?d -1 ), ASA (36 mg?kg -1 ?d -1 ) and equal placebo solution respectively.Eight days later all rats were given anesthesia and blood was taken from abdominal aorta with a plastic catheter, then the indexes related to blood hemodynamics,coagulation and blood fibrinolysis were measured. Twenty four SD rats were treated in the same way mentioned above. Platelet aggregation was measured by turbidimetric method. Plasma level of cyclic GMP and prostacyclin was evaluated by radioimmunoassay and nitric oxide by spectrophotometric determination. Common carotid artery-external jugular vein bypass was established in another 24 rats, and the weight of wet thrombus was measured with high sensitive electrical scale. RESULTS In group of Arg-Glu, statistically significance decrease versus placebo group was observed on blood apparent viscosity, reduced viscosity, hematocrit and plasma viscosity, increase versus placebo was also observed on blood reciprocal calcium time, activated partial thromboplastin time and prothrombin time ( P 0 05). Platelet aggregation activation decreased compared with placebo 〔(0 75%?3.62%) vs (32 8%?6 62%) P 0 05)〕. CONCLUSION Arg-Glu with its properties of antiplatelet、anticoagulation and improvement of blood rheology status in rats could be regarded as one antiplatelet drug and one NO precursor .Its mechanism of action was thought to be by Arg-NO-cGMP metabolism pathway while other mechanism might be involved.