ABSTRACT
AIM: To study the effects of metformin on the pressure overload-induced cardiac hypertrophy in rats. METHODS: Transverse aortic constriction (TAC) model of rat was made through laparotomy. One week after TAC surgery, the rats were randomly divided into 5 groups (n=8 in each group) and were administered with the corresponding drugs orally every day for 8 weeks: sham group (sham surgery, administered with 2 mL distilled water);TAC group (TAC rats, administered with 2 mL distilled water);metformin(MET) group (TAC rats, administered with MET at dose of 300 mg·kg~(-1)·d~(-1));MN group [TAC rats, administered with MET at dose of 300 mg·kg~(-1)·d~(-1) plus NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) 50 mg·kg~(-1)·d~(-1)] and L-NAME group (TAC rats, administered with L-NAME at dose of 50 mg·kg~(-1)·d~(-1)). After treated for 8 weeks, the echocardiography, hemodynamics, the ratio of heart weight to body weight (HW/BW) and histological examination of the heart were performed. The levels of myocardial AMP-activated protein kinase subunit α (AMPKα), p-AMPKα~(Thr172), endothelial nitric oxide synthase (eNOS) and p-eNOS~(Ser1177) were detected by Western blotting. Plasma and myocardial nitric oxide (NO) were detected biochemically. RESULTS: After 8 weeks treatment, the wall thickness of left ventricle, the heart weight/body weight ratio (HW/BW), and the left ventricular myocardial perivascular fibrosis and myocardial interstitial fibrosis of the animals in TAC group were significantly increased as compared to those in sham rats. Treatment with MET for 8 weeks significantly attenuated left ventricular hypertrophy and improved cardiac function in TAC rats. These effects of MET were mostly abolished by L-NAME. Molecular biology and biochemical testing revealed that the levels of left ventricular myocardial p-AMPKα~(Thr172) and p-eNOS~(Ser1177), as well as the levels of myocardial and serum NO were significantly increased in MET group. CONCLUSION: Long-term MET treatment significantly inhibits the cardiac hypertrophy and the myocardial fibrosis and improves the cardiac functions in pressure-overload rats. The anti-hypertrophic effects of MET may be mediated via activation of AMPK-eNOS signaling pathway.
ABSTRACT
[Objective]This study was designed to investigate the effects of 5-aminoimidasole-4-carboxamide ribonucleoside (AICAR)on activity of transcription factor Forkhead O 3a(FOXO3a)and expression of ubiquitin ligase muscle atrophy F-box (MAFbx),and to explore the role of adenosine monophosphate-activated protein kinase(AMPK)on proteolysis pathways in eardiomyocytes.[Methods]The effect of AICAR on activation of AMPK was observed.Cultured neonatal rat cardiomyocytes was treated with AICAR in different concentration.Cultured cardiomyocytes were then divided into three groups:control group,AICAR group,AICAR+Compound C group.Effects of AMPK activation on phosphorylation of FOXO3a and expression of MAFbx in cardiomyocytes were detected using Western blot.[Results]①Compared with control group,activity of AMPK in cultured cardiomyocytes was increased after treatment with 0.25 mmol/L or 0.5 mmol/L AICAR for 6 h(P＜0.05),and the activity of AMPK was further enhanced after treatment with 1.0 mmol/L or 2.0 mmol/L AICAR for 6 h(P＜0.01).②Activation of AMPK by AICAR significantly increased the transcriptional activity of FOXO3a(P＜0.01),and enhanced MAFbx protein expression in cardiomyocytes when comparing with control group(P＜0.01),however,specific AMPK antagonist Compound C markedly reversed these effects induced by AICAR.[Conclusion]AMPK may regulate cardiomyocytes proteolysis by activation of FOXO3a transcription factor,and up-regulation of MAFbx protein expression.
ABSTRACT
Diagnostics is the bridge of basic medicine and clinical medicine.Teaching method with the idea of evidence-based medicine is benefit to cultivate the students' ability on clinical practice.To establish this educational mode,teachers should learn a teaching method guided by ideas of evidence-based medicine,and students should be taught a tool for solving clinical problems with ideas of evidence-based medicine.
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BACKGROUND: The emphasis for preventing and treating cardiovascular diseases is to detect correlated risk factors. Among those accepted risk factors, whether serum uric acid (SUA) plays an independent role in the development of diseases is unknown.OBJECTIVE: To study SUA distribution and the prevalence of hyperuricemia, in middle-aged and elderly residents from the conjoining area between city and countryside in Guangzhou, and its association with other cardiovascular disease risk factors.DESIGN: Cross-sectional study.SETTING: Department of Cardiovascular internal medicine, Prevention and Health department, the Third Affiliated Hospital of Sun Yat-sen University.PARTICIPANTS: An investigation on the risk factors of cardiovascular diseases was carriedout among total 890 residents living at the conjoining area between city and countryside in Guangzhou in December 2002. A total of 642 persons including 152 men and 490 women who were above 55years and had complete data were involved, and all of them understood and agreed to the investigation.the-spot investigation. Systolic pressure, diastolic pressure, body height and body mass were measured, and then body mass index [body mass (kg)/body height (m)2] was calculated. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride and total cholesterol were measured by endpoint method; SUA was measured by uricolase turbidimetric method.were defined as hyperuricemia. Diagnosis of hypertension was made according to the WHO/ISH 1999 Prevention and Cure Guidelines of Hypertension. Various kinds of dyslipidemia were diagnosed based on Prevention and Cure suggestions of dyslipidemia for Chinese (1997). Obesity was defined, according to 2002 International Obesity Special Working Group'skewness distribution and described by Median ± quartile. Spearson correlation analysis was used to determine the dependability between SUA and other selected cardiovascular risk factors. Binary Logistic regression analysis was done for further analysis.SUA and other cardiovascular risk factors.terolemia and hypertriglyceridemia in men and women were 30.3%, 30.8%;were (357.30±66.77) and (299.80±59.64) μmol/L respectively. SUA level was positive correlated with age in women (r=0.18, P ＜ 0.01), but was not of SUA in men were 293.53, 357.30, 427.08 (μmol/L), and in women were 247.60, 299.80, 366.88 (μmol/L). Low-density lipoprotein cholesterol, total cholesterol, triglyceride, blood pressure and body mass index were positively associated with SUA, while high-density lipoprootein cholesteral was negtive correlated with SUA. In both men and women, triglyceride, total cholesterol, systolic blood pressure and body mass index were positively correlated with SUA significantly (r=0.09-0.35, P ＜ 0.05-0.01), but highdensity lipoprotein cholesterol was negatively correlated with SUA significantly (r=-0.21, -0.25, P ＜ 0.05, 0.01); diastolic blood pressure in men and low high-density lipoprotein cholesterol in women were positively correincluded to Logistic regression equation were age, body mass index and triglyceride [OR (95%CI): 1.048 (1.023-1.073), P=0.000; OR (95%CI): 1.156(1.096-1.219), P=0.000; OR (95%CI): 1.436 (1.224-1.684), P=0.000].uricemia is correlated with hypertension and various kinds of dyslipidemia.The elevation of SUA may be an important marker of cardiovascular dismay affect SUA mostly, and increase the risk for hyperuricemia.