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OBJECTIVES@#To explore the expression of autophagy related genes 5 (ATG5) and cyclin E in coronary heart disease (CHD) and its clinical significance.@*METHODS@#From April 2018 to August 2018, 80 patients diagnosed with CHD in the Second Xiangya Hospital, Central South University were selected as an observation group, and another 80 healthy subjects were selected as a control group. The expression of ATG5 and cyclin E mRNA in nucleate cells and the plasma protein in the 2 groups were detected and analyzed. The model of macrophage-derived foam cells induced by oxidized low density lipoprotein (ox-LDL) was used to simulate atherosclerosis. The proliferation of macrophage- derived foam cells and the protein levels of ATG5 and cyclin E induced by ox-LDL at different concentrations were examined.@*RESULTS@#Compared with the control group, the levels of ATG5 mRNA and protein in the blood in the observation group were decreased, and the cyclin E mRNA and protein levels were increased, there were statistically difference (both <0.05). Receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of ATG5 mRNA, cyclin E mRNA, ATG5 protein and cyclin E protein were 0.739, 0.780, 0.671 and 0.807, respectively. Pearson analysis showed that the ATG5 mRNA was negatively correlated with the cyclin E mRNA (=-0.734, <0.05),while the plasma ATG5 protein was negatively correlated with the plasma cyclin E protein (=-0.746, <0.05). Macrophage-derived foam cell model induced by ox-LDL showed that the proliferation of foam cells and the expression levels of cyclin E protein were increased in a concentration and time-dependent manner, and the expression levels of ATG5 protein were decreased in a concentration-dependent manner.@*CONCLUSIONS@#The levels of ATG5 mRNA and protein are lowly expressed while the levels of cyclin E mRNA and protein are highly expressed in the patients with CHD.The ATG5 protein levels are lowly expressed in ox-LDL-treated macrophage-derived foam cells while the cyclin E protein levels are highly expressed in ox-LDL-treated macrophage-derived foam cells. Based on these observations, we conclude that ATG5 inhibits the degradation of the cyclin E and promotes the proliferation of macrophages, involving in the occurrence and development of CHD.
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Humans , Autophagy , Autophagy-Related Protein 5 , Coronary Disease , Cyclin E , Foam Cells , Lipoproteins, LDLABSTRACT
Objective To investigate the effect of chronic intermittent hypoxia(CIH)on serum high-density lipoprotein cholesterol(HDL-C)and the changes of HDL-C metabolism-related indicators such as the expressions of peroxisome proliferators-activated receptor a (PPARα)and adenosine triphosphate binding cassette transporterA1(ABCA1)in liver in male SD rats.Methods Obstructive sleep apnea syndrome(OSAHS)-induced CIH rats were randomly allocated into 6 groups:10％CIH-3 weeks,5％CIH-3 weeks,5％CIH-3 weeks +RH(Removal of hypoxia-3 weeks),10％CIH-3 weeks + RH(Removal of hypoxia-3 weeks),control group-3 weeks,and control group-6 weeks.Serum lipids were measured and compared.To observe and compare the liver pathology,the expression levels of PPARα and ABCA1 in liver tissue of CIH rats were detected by immunohistochemical method.Results The levels of serum TC,TG and LDL-C was significantly higher in CIH rats than in control group.The levels of TC,TG and LDL-C were significantly lower in reoxygenation groups than in CIH groups.There was no significant difference between experiment groups and correspondent control groups(all P＞0.05).Compared with control group,CIH rats had significantly lower levels of serum HDL-C;Compared with CIH groups,the levels of HDL-C were significantly higher in reoxygenation groups.There was no significant difference between experiment groups and correspondent control groups(all P＞0.05).Compared with control group,the expression of PPARα and ABCA1 of CIH group was significantly lower;Compared with CIH groups,the expression of PPARα and ABCA1 was significantly higher in reoxygenation groups;There was no significant difference in the expression of PPARα and ABCA1 between reoxygenation groups and correspondent control groups,in which the oxygen level was recovered to normal.Conclusions The serum HDL-C level was obviously decreased in OSAHS-induced CIH rats,and the decreased serum HDL-C can be effectively improved by reoxygenation intervention.OSAHS-induced CIH may lead to the dyslipidemia through PPARα-ABCA1 pathway,and reoxygenation intervention for three weeks can effectively recover the expression levels of PPARα and ABCA1 to normal levels,which suggests that if CIH is effectively intervented,the change of PPARα and ABCA1 of liver can be reversed,thereby reversing dvslipidemia.
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Objective: To investigate the effect of chronic intermittent hypoxia (CIH) on liver injury and the expression of fractalkine in rats and explore its possible mechanism. Methods: A CIH murine model was established to mimic the pathophysiology of obstructive sleep apnea-hypopnea syndrome (OSAHS) in humans. Thirty healthy male Spraque-Dawley rats were randomly assigned to 3 groups: a 5% CIH group, a 5% CIH+RH (removal of hypoxia) group and a control group ( 10 rats in each group). The 5% CIH and 5% CIH+RH groups were exposed to CIH for 3 weeks, 8 h/d, and the frequency of hypoxia was 20 times/h. The 5% CIH+RH group was then exposed to normal gaseous environment for another 3 weeks. After the experiment, liver sections were stained with hematoxylin-eosin (HE) and the liver pathology was observed. The expression of fractalkine in the liver tissues was detected by immunohistochemical method. Results: 1) Compared with the control group, the hepatic steatosis and inflammatory activities in the 5% CIH and 5% CIH+RH groups were more severe (allP Conclusion: CIH can induce liver injury and high fractalkine expression in rat liver tissues.
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OBJECTIVE@#To investigate the effect of nasal intermittent positive pressure ventilation (NIPPV) on N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and type II respiratory failure.@*METHODS@#Forty patients with AECOPD and type II respiratory failure and 40 patients with stable phase chronic obstructive pulmonary disease were randomly assigned into study. Plasma levels of NT-proBNP, arterial blood gas, APACHE II scores, and pulmonary artery pressures were measured. The plasma level of NT-proBNP was compared between the two groups. Effect of NIPPV on NT-proBNP was studied in patients with AECOPD and type II respiratory failure.@*RESULTS@#There were negative correlations between NT-proBNP and pH, and between NT-proBNP and PaO2 (r=-0.691,r=-0.704,respectively;P<0.001),positive correlations between NT-proBNP and PaCO2, and between NT-proBNP and APACHE II scores (r=0.774, r=0.810, respectively, P< 0.001), and positive correlation between NT-proBNP and PAP (r=0.965, P<0.001) in all patients. In patients with AECOPD and type II respiratory failure, there were negative correlations between NT-proBNP and pH,and between NT-proBNP and PaO2 (r=-0.636, r=-0.616,respectively; P<0.001); there were positive correlations between NT-proBNP and PaCO2, and between NTproBNP and APACHE II scores (r=0.545, r=0.475, respectively; P=0.001, P=0.002); and there were positive correlation between NT-proBNP and pulmonary artery pressure (r=0.833,P<0.001). The plasma levels of NT-proBNP were significantly higher in patients with AECOPD and type II respiratory failure than in control subjects [(939.60 ± 250.00) pg/mL vs (151.55 ± 111.20) pg/mL;P<0.01]. NIPPV decreased plasma levels of NT-proBNP [(229.15 ± 98.26) pg/mL vs (939.60 ± 250.00) pg/mL; P<0.01] in patients with AECOPD and type II respiratory failure, as well as improved arterial blood gas and APACHE II scores. Although NIPPV appeared to decrease pulmonary artery pressure somewhat between pre-treatment and post-treatment groups, the differences were not statistically significant (P=0.056).@*CONCLUSION@#The plasma level of NT-proBNP reflects the severity of patients with AECOPD and type II respiratory failure. NIPPV can decrease a patient's splasma level of NT-proBNP, which has clinical value for evaluating the effect of NIPPV.
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Aged , Female , Humans , Male , Middle Aged , Blood Gas Analysis , Natriuretic Peptide, Brain , Blood , Peptide Fragments , Blood , Positive-Pressure Respiration , Methods , Pulmonary Disease, Chronic Obstructive , Blood , Therapeutics , Respiratory Insufficiency , Blood , TherapeuticsABSTRACT
OBJECTIVE@#To observe the effects of two different hypoxia patterns on blood pressure and the underlying mechanisms.@*METHODS@#Eighteen male SD rats were randomly divided into three groups: the intermittent hypoxia group (IH group), the continuous hypoxia group (CH group) and the normal control group (NC group). The rats of the IH and CH group were subjected to intermittent hypoxia (7 h/d) and continuous hypoxia (7 h/d) for 42 days respectively. The NC group rats were untreated. The levels of arteria caudilis systolic pressure (ACSP) were measured with noninvasive rats arteria caudilis gauge before the experiment, at the end of 3rd, 6th week of the experiment. The concentrations of norepinephrine (NE) in serum and neuropeptide Y (NPY) in plasma were respectively measured by enzyme-linked-immunosorbent assay (ELISA) and radioimmunoassay. The contents of malondialdehyde (MDA) and the ability of inhibiting hydroxyl free radical in serum were analyzed by thiobarbituric acid colorimetric analysis (TBAR) at the end of 6th week.@*RESULTS@#At the end of 3rd week, the levels of ACSP were considerably higher than those before the treatment (P0.05). The levels of NE, NPY and MDA were positively related with ACSP (r=0.873, P<0.01; r=0.671, P<0.01; r=0.582, P<0.05). The correlation between the ability of inhibiting hydroxyl free radical and ACSP was negative (r=-0.790, P<0.01). the concentrations of MDA were positively related with NE and NPY respectively (r=0.843, 0.777, P<0.01) and the ability of inhibiting hydroxyl free radical was negatively related with NE and NPY respectively (r=-0.864, -0.717, P<0.01).@*CONCLUSION@#Intermittent hypoxia can induce high blood pressure, which may be related to the sympathetic over-activity and the oxidative stress.
Subject(s)
Animals , Male , Rats , Blood Pressure , Physiology , Hypoxia , Classification , Oxidative Stress , Physiology , Rats, Sprague-Dawley , Sympathetic Nervous SystemABSTRACT
Objective To screen and diagnose obstructive sleep apnea-hypopnea syndrome (OSAHS) in elderly males by obesity index using receiver operating characteristic(ROC) curves. Methods Data of 402 consecutive elderly male patients who underwent polysomnography from 2001 to 2008 were collected. The relationship between apnea hypopnea index(AHI) and obese indexes such as body mass index (BMI), neck circumference (NC), waist circumference (WC) and waist-to-hip ratio (WHR) were analyzed by Pearson's correlation. ROC curves were used to determine the best cutoff values to screen and diagnose OSAHS, and their priority was compared by area under curve (AUC). A two-tailed P value less than 0.05 was considered statistically significant. Statistical analysis was carried out with SPSS version 13.0. Results (1) AHI was positively correlated with BMI (r=0.241,P<0.001), NC(r=0.201,P<0.001), WC(r=0.210,P<0.001) and WHR(r=0. 097,P>0.05)) in elderly male patients. The area under curve (AUC) of BMI, NC, WC and WHR was 0.61, 0.58, 0.51 and 0.45 respectively, and P value was 0.001,0.060,0.840 and 0. 250 respectively. Only BMI was competent in screening and diagnosing OSAHS in elderly male adults; (2) The optimal value of BMI was 22.0 kg/m~2 in screening OSAHS with specificity 90% and rate of missed diagnosis 10%; (3) The optimal value of BMI was 29.0 kg/m~2 in diagnosing OSAHS with specificity 90% and rate of missed diagnosis 10%. Conclusions BMI more than 22.0 kg/m~2 could be the reference standard to screen OSAHS and BMI more than 29.0 kg/m~2 to diagnose OSAHS in elderly men.