[A study of the related pathways of oxidative stress in chronic intermittent hypoxia rats and the effect of N-acetylcysteine].

OBJECTIVE: To study the relation of oxidative stress with systolic blood pressure (SBP) and renin-agiotensin system (RAS) in a rat model of chronic intermittent hypoxia (CIH), and to investigate the preventive effect and mechanism of N-acetylcysteine (NAC) in CIH-induced hypertension. METHODS: Twenty-four male Sprague-Dawley (SD) rats were divided into 4 groups: CIH+NAC group (CIH1), CIH+normal saline (NS) group (CIH2), CIH control group (CIH3) and blank control group (UC). CIH rats were subjected to alternating cycles of hypoxia (6%-8% O2 in N2 for 20-25 s) and normoxia (21% O2 in N2 for 2 min) every 180 s for 7 h per day. Rats in the CIH1 group were treated with NAC (800 ml×kg(-1)×d(-1)) by intraperitoneal injection, and those in the CIH2 group were treated with NS (5 ml×kg(-1)×d(-1)). RESULTS: SBP in the CIH2 and CIH3 groups at the end of 6th week was significantly elevated compared with the baseline SBP (P<0.001) and those in the CIH1 and the UC groups (P<0.05). The expression of angiotensin-converting enzyme (ACE) and ACE2 in renal arterioles was significantly different (P<0.05), and the levels of angiotensin II (AngII) in the serum and kidney tissues, oxidation of low density lipoprotein (ox-LDL) and malondialdehyde (MDA) in the serum were increased. Ang-(1-7) and the inhibitory capability for hydroxyl free radicals in the serum were decreased significantly in CIH2 and CIH3 groups compared with CIH1 and UC (P<0.05) groups at the end of 6th week. SBP showed a positive correlation with AngII in serum and kidney tissues, but showed a negative correlation with Ang-(1-7) in serum and kidney tissues. The levels of MDS and ox-LDL in serum showed a positive correlation with AngII in serum and kidney tissues respectively, but showed a negative correlation with Ang-(1-7) in serum and kidney tissues respectively. The inhibitory capability for hydroxyl free radicals in serum showed a positive correlation with Ang-(1-7), but a negative correlation with AngII. The level of ox-LDL showed a positive correlation with MDA, but a negative correlation with the inhibitory capability for hydroxyl free radicals. There were no significant difference between CIH1 and UC groups in parameters except of SBP and AngII (P<0.05). All the data were not different between CIH2 and CIH3 groups (P>0.05). CONCLUSIONS: CIH caused oxidative stress and RAS imbalance in rats. The imbalance of RAS in CIH rats was related with oxidative stress. The imbalance of RAS and oxidative stress may be one of the important mechanisms for CIH-induced hypertension. NAC can prevent CIH-induced hypertension through modulation of RAS by its anti-oxidative effect.

[Construction of a subtracted cDNA library of chronic intermittent hypoxia rabbit liver by suppression subtractive hybridization].

OBJECTIVE: To construct a subtracted cDNA library of chronic intermittent hypoxia (CIH) rabbit liver by suppression subtractive hybridization (SSH). METHODS: Twenty-four rabbits were divided into 4 groups: ordinary feeding group, full-fat food group, ordinary feeding in chronic intermittent hypoxia group, and full-fat food in chronic intermittent hypoxia group. The mRNAs were extracted from different rabbit livers and converted into double-strand cDNA. After digestion with restriction enzyme, the cDNA of hyperlipidemia-sensitive rabbit group was subdivided into 2 portions and each one was lighted with different adaptors. Two rounds of both hybridization and suppression PCR obtained the differentially expressed cDNA. The PCR products were inserted into T/A vector to set up the subtractive cDNA library. The clones were selected and amplified by PCR and identified. RESULTS: Based on the pathology of the abdominal aorta and liver, and the amplified library contained 500 positive bacteria clones, including 462 clones, which had inserts from 250 to 700 bp by PCR analysis. A novel rabbit gene, Cthrc1, involved in CHI had been cloned. The GenBank Accession Number is XM_418373. CONCLUSION: The molecular mechanism of CIH promoting atherogenesis formation is made clear.

[Effects of nasal continuous positive airway pressure short-term treatment on C-reactive protein and intercellular adhesion molecule-1 in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investgate the effects of nasal continuous positive airway pressure (nC-PAP) short-term treatment on the serum level of C-reactive protein (CRP) and intercellular adhesion molecule-1 in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. METHODS: Twenty patients with OSAHS ( AHI > or = 15 ) and 15 controls (AHI < 15) were recruited. After polysomnography (PSG), the venous blood was collected from all subjects to investigate CRP and ICAM-1. The effects of short-term treatment (4 d) of nCPAP on the serum levels of CRP and ICAM-1 were studied in patients with moderate and severe OSAHS. RESULTS: Before the treatment, there was a significant positive correlation between CRP and AHI in all subjects (r = 0.615, P < 0.001), a significant negative correlation between CRP and the mean nocturnal oxygen saturation (r = -0.682, P < 0.001), and a significant negative correlation between CRP and the lowest nocturnal SaO2 (r = -0.61, P < 0.001). There was a significant positive correlation between ICAM-1 and AHI in all subjects (r = 0.751, P < 0.001), a significant negative correlation between ICAM-1 and the mean nocturnal oxygen saturation (r = -0.68, P < 0.001), and a significant negative correlation between ICAM-1 and the lowest nocturnal oxygen saturation (r = -0.656, P < 0.001). There was a significant positive correlation between CRP and ICAM-1 (r = 0.437, P = 0.009). The levels of CRP and ICAM-1 were significantly higher in patients with moderate and severe OSAHS than in the controls (P < 0.01). nCPAP decreased the levels of CRP and ICAM-1 in patients with moderate and severe OSAHS (P < 0.01). CONCLUSION: Inflammatory reaction exists in OSAHS and can be palliated after nCPAP short-term treatment.

[Influence of obstructive sleep apnea-hypopnea syndrome on the QTc interval].

OBJECTIVE: To investigate the influence of obstructive sleep apnea-hypopnea syndrome (OSAHS) on the QTc interval. METHODS: By the polysomnograph,98 patients were divided into an obstructive sleep apnea-hypopnea syndrome group and a control group. We tested their 24 hour DCG and observed the difference of the heart rate,QT interval and QTc interval at the same time. RESULTS: We compared the heart rate (76 +/- 10 bt/min), QT interval (366 +/- 30 ms), and QTc interval (404 +/- 45 ms) with those of the control group (73 +/- 96 bt/min, 342 +/- 31 ms, 374 +/- 30 ms, respectively). The QT interval and QTc interval significantly differred (P < 0.05). CONCLUSION: The QT interval and QTc interval in the OSAHS group has been prolonged, suggesting OSAHS might be a high risk factor in arrhythmia and sudden death.

Effect of atorvastatin on serum oxidative stress and N-terminal brain natriuretic peptide expression in rats.

OBJECTIVE: To investigate the effect of atorvastatin on serum oxidative stress and N-terminal brain natriuretic peptide expression in rats. METHODS: A total of 40 healthy male SD rats were randomly divided into the sham group (Group A, n=10, saline 5 mL/d), ischemia-reperfusion group (Group B, n=10, saline 5 mL/d), atorvastatin group (Group C, n=10, atorvastatin 20 mg/kg · d), atorvastatin + N-amino-arginine group (Group D, n=10, atorvastatin 20 mg/kg · d + N-amino arginine 15 mg/kg). Myocardial ischemia-reperfusion rat model was established after 3 days of gavage. N-amino arginine 15 mg/kg was given by tail vein injection 15 min before ischemia. After reperfusion, enzymology indicators such us creatine kinase (CK) and lactate dehydrogenase and the oxidative stress parameters such as nitric oxide (NO), malondialdehyde (MDA) and total superoxide dismutase (TSOD), and n-terminal pro-brain natriuretic peptide (NT-proBNP) expression was detected by immunohistochemistry. RESULTS: LDH and CK levels of group A were significantly lower than the other three groups, and group B was the highest. There was significant difference between group B and group C (P<0.05), and no significant difference between group B and group D (P>0.05). MDA levels in group B were significantly higher than the other three groups. The lowest was group A, followed by group C, the difference among groups was significantly (P<0.05). TSOD and NO levels in group B was the lowest, the level in group A was the highest, followed by group C, the difference among groups was significant (P<0.05). NT-proBNP level in group B was significantly higher than the other three groups, the lowest was group A, followed by group C, the difference among groups was significant (P<0.05). CONCLUSIONS: Atorvastatin has a protective effect on the myocardial injury in the myocardial ischemia and reperfusion rats. It can increase NO synthesis and decrease MDA content, increase serum TSOD activity and the oxidative stress effect, meanwhile protect myocardial cells and reduce myocardial injury.

[Evaluation on the accuracy of obese indexes in predicting obstructive sleep apnea-hypopnea syndrome in male adults].

OBJECTIVE: To determine the best cutoff value and reference standard of obese indexes and to compare their diagnostic value in screening, predicting and diagnosing obstructive sleep apnea-hypopnea syndrome (OSAHS) in male adults by receiver operating characteristic curve (ROC). METHODS: A total of 1110 male adults were included and cross-sectional study was adopted. Four parameters including: body mass index (BMI), neck circumference (NC), waist circumference (WC) and waist-to-hip ratio (WHR) were studied. The correlativity between apnea-hypopnea index (AHI) and BMI, NC, WC and WHR were analyzed by pearson correlation test. ROC curve was used to assess the diagnostic value and determine their best cutoff value to predict OSAHS and reference standard to screen/diagnose it. Their conformity in predicting OSAHS was analyzed by area under curve (AUC). SPSS software version 13.0 was used for statistical analysis and P< or =0.05 was considered to indicate statistical significance. RESULTS: (1) All of the fourindexes (BMI, NC, WC and WHR) showed a significantly positive correlation with AHI in adult male patients, with their Pearson coefficients as 0.373, 0.276, 0.291 and 0.127, respectively, and their P value were all below 0.001; (2) The best cutoff value of BMI, NC and WC in predicting OSAHS were 26.5 kg/m2 , 39 cm, 95 cm, and their corresponding sensitivity rates were 54%, 57% and 64% while rates of specificity as 73%, 65% and 53%; (3) BMI was better than other two indexes in predicting OASHS in adult male patients; (4) The value of BMI, NC and WC in screening OSAHS among adult male patients with 90% sensitivity and 10% rate of missed diagnosis as 23 kg/m2, 35 cm, 85 cm; (5) The value of BMI, NC and WC in screening OSAHS in adult male patients with 90% specificity and 10% misdiagnosis rate as 29 kg/m2, 43 cm, 105 cm, respectively. CONCLUSION: BMI seemed better in predicting OSAHS in male adults than NC, WC and WHR. The best cutoff values to predict OSAHS of BMI, NC and WC were 26.5 kg/m2, 39 cm and 95 cm, respectively. Their reference standards to screen OSAHS were 23 kg/m2, 35 cm and 85 cm while 29 kg/m2, 43 cm and 105 cm to predict OSAHS.

[Characteristics of the sleep apnea syndrome in the aged].

OBJECTIVE: To study the characteristics of the sleep apnea syndrome in the aged. METHODS: Forty-two males who were suspicious of the sleep apnea syndrome (SAS) were detected with 7-hour polysomnography (PSG). RESULTS: The body mass index (BMI) and neck circumference showed no significant difference in the aged and middle aged groups. The apnea/hypopnea index (AHI) and microarousal index (MAI) were significantly lower, and the minimum oxygen saturation (SaO2) significantly higher in the aged than those in the middle aged (P < 0.05). Age was negatively correlated to AHI (r = -0.329, P < 0.05). The BMI and neck circumference were positively correlated to AHI (r = 0.326, P < 0.05; r = 0.306, P < 0.05, respectively). CONCLUSION: SAS patients are less severe in the aged excluding the affection of the BMI and neck circumference.