OBJECTIVE: To investigate the effects of Naohuandan Recipe on learning and memory abilities of SAM-P/8 mice and its role in anti-oxidation and anti-apoptosis. METHODS: Forty SAM-P/8 mice were randomly divided into four groups, which were untreated (normal saline-treated) group, Yinkeluo Tablets (extracts of gingko leaf)-treated group, low-dose Naohuandan Recipe-treated group and high-dose Naohuandan Recipe-treated group. Mice in these groups were given corresponding drugs orally for 105 days. Then the performances of learning and memory of mice were tested by a step-down passive avoidance task and a Y-maze test. The serum levels of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were detected. The expression level of bcl-xl mRNA in cerebral cortex and hippocampus of mice was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The performances of learning and memory in the Yinkeluo Tablets-treated group, low- and high-dose Naohuandan Recipe-treated groups were significantly improved as compared with those in the untreated group (P<0.05 or P<0.01), and such performance was the best in the high-dose Naohuandan Recipe-treated group among these four groups (P<0.01). The serum levels of SOD and GSH-Px and the expression of bcl-xl mRNA in cerebral cortex and hippocampus of mice in the Yinkeluo Tablets-treated group, low- and high-dose Naohuandan Recipe-treated groups were also significantly higher than those in the untreated group (P<0.05 or P<0.01), while the serum level of MDA in the untreated group was higher than that in the other three groups (P<0.01). CONCLUSION: Naohuandan Recipe can improve learning and memory abilities of SAM-P/8 mice, and this effect may be related to its anti-oxidation efficacy and enhancement of expression level of bcl-xl mRNA.

ObjectiveTo investigate the effect of the levels of serum lipid on the prognosis of patients with severe heart failure.MethodsThe clinical data of 149 patients with severe heart failure was analyzed retrospectively,the levels of serun lipid were compared among different causes and different NYHA cardiac functional grading patients.And the prognosis was compared between low-serum lipid and non-low-serum lipid patients.Results There were significant differences in the levels of total cholesterol(TC),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),albumin (ALB) among different NYHA cardiac functional grading (P ＜0.05),but there was no significant difference in triacylglycerol (TG) among different NYHA cardiac functional grading(P ＞ 0.05 ).The levels of TC,HDL-C,LDL-C in dilated cardiomyopathy and rheumatic heart disease were lower than those in coronary heart disease combined with hypertension and ischemic cardiomyopathy,there were significant differences (P ＜0.05).Followed up for 2 years,the mortality,deteriorated frequency,hospitalization frequency more than 2 times a year and hospitalization time more than 1 month in low-serum lipid patients [29.0％ (9/31 ),25.8％ ( 8/31 ),48.4％ ( 15/31 ),61.3％ ( 19/31)]were higher than those in non-low-serum lipid patients [9.3 ％ ( 11/118 ),9.3％ ( 11/118 ),17.8％ (21/118 ),24.6％ (29/118 )],and there were significant differences (P ＜ 0.01 or ＜0.05).Conclusions For patients with severe heart failure,NYHA cardiac functional grading has significantly negative correlation with their serum lipid levels.Lower serum lipid levels will seriously affect the prognosis of patients.

[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.

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.

Objective To explore the efficacy of recombinant human brain natriuretic peptide (rhBNP) in the treatment of heart failure patients with coronary heart disease (CHD).Methods Ninety-six CHD patients with heart failure were divided into observation group (48 cases) and control group (48 cases) by random digits table,and rhBNP was used in observation group and nitroglycerin was used in control group.The efficacy,left ventricular ejection fraction (LVEF) and urine output in two groups were observed.Results The total effective rate in observation group was 93.75％ (45/48),and 81.25％ (39/48) in control group,there was significant difference between two groups (P ＜ 0.05).LVEF and urine output after treatment were better than those before treatment [observation group:(57.7 ± 3.9)％ vs. (32.5 ± 3.1 )％,(70.5 ± 31.1 ) ml/h vs.(34.5 ± 13.7) ml/h;control group:(52.2 ± 3.3)％ vs.(33.4 ± 2.9)％,(53.6 ± 23.4) ml/h vs.(33.8 ± 13.4)ml/h,P ＜ 0.05 ].After treatment,LVEF and urine output in observation group were higher than those in control group (P ＜ 0.05 ).Incidence of adverse reaction in observation group was lower than that in control group [ 18.75％ (9/48) vs.35.42％ ( 17/48),P ＜ 0.05 ].Conclusion rhBNP has curative effect and small adverse reactions on CHD patients with heart failure,and can significantly improve the patients' general condition.

BACKGROUND: Recent study showed that osteocalcin may elevate Insulin secretion and sensitivity, prevent the fat accumulation, play a role in the metablism of glucose and lipid. Undercarboxylated osteocalcin works as the main role. OBJECTIVE: To investigate the effect of different concentrations of glucose on osteoblast undercarboxylated osteocalcin. METHODS: The rib trabeculae were resected and broken, trypsinizated and washed completely by PBS. Bone surface and non-adhesive floating cells in cleaning fluid were observed with inverted microscope. Rib trabeculae was washed by DMEM culture medium once, and cultured in culture bottle. The culture liquid was replaced by new one once a week. The osteoblast was moved from the scledte a week later. The cells were fused monolayer and could be subcultured 4 to 6 weeks later. The active second or third generation cells were inoculated to 6-pore plate forming 5 groups. Osteoblast were stimulated by 5.6 mmol/L., 7.6 mmol/L, 9.6 mmol/L, 12.6 mmol/L, 20.6 mmol/L glucose medium respectively after the 80% cells were fused, the vitamin K_2 was added into the culture liquid until the concentration of it to be 10~(-5) mol/L. Supernatant was collected after half hour culturing, the undercarboxylated osteocalcin level were detected with RIA test kit, and corrected it as the total the undercarboxylated osteccalcin, calculated the carboxylated incomplete osteocalcin rate. RESULTS AND CONCLUSION: The rate of ostecblast carboxylated incomplete osteocalcin was different under different concentration glucose. The rate of 7.6 mmol/L, 9.6 mmol/L, 20.6 mmol/L concentration glucose groups were higher than that of 5.6 mmol/L glucose group [(0.27±0.02)%, (0.29±0.04)%, (0.12±0.02)%, P < 0.05]. It is indicated that osteoblast could sense the change of glucose concentration by regulating the secretion of the undercarboxylated osteocalcin between the concentration of 5.6mmol/L to 9.6mmol/L, while the carboxylated incomplete osteocalcin decreased as the concentration of glucose increased.

Objective To explore relationship between the nature of carotid atherosclerotic plaque and the number and function of endothelial progenitor cells in peripheral blood.Methods A prospective study of 80 carotid atherosclerotic plaque patients were selected from June 2016 to March 2017 in Guangdong Second Provincial General Hospital.All patients were examined with Cranial magnetic resonance imaging or X-ray computed tomography,pathological examination,carotid artery color Doppler ultrasonography.Patients were divided into hard plaque group (n =42) and soft plaque group (n =38) according to the nature of carotid atherosclerotic plaque.Forty healthy subjects were selected as controls.Monocytes were obtained from 10 ml of elbow venous blood by density gradient centrifugation.Adherent cells were cultured and identified by confocal laser microscopy.The number,migration,proliferation and adhesion of EPCs in soft plaque group and hard plaque group were evaluated.Results The number of proliferating cells (0.847 ± 0.037),migrating cells(27.697±8.248) and adherent cells (46.184± 7.876) in the normal control group were significantly higher than those in the hard plaque group ((0.647±0.019),(18.643±3.289),(32.165±4.325)) and the soft plaque group ((0.679± 0.023),(23.576± 6.327),(40.587±6.523)) (all P＜ 0.001),while the proliferation,migration and adherent cells in the hard plaque group were lower than those in the soft plaque group (all P＜0.001).Conclusion The nature of carotid atherosclerosis plaque is closely related to the number and function of endothelial progenitor cells in peripheral blood.The number of endothelial progenitor cells in carotid atherosclerosis patients with hard plaque is small,and their proliferation,migration and adhesion ability are impaired.