Objective To explore the mechanism of chronic intermittent hypoxia (CIH) on renal damage with normal diet and high-fat diet. Methods Twenty-four healthy male Wistar rats of SPF grade were randomly divided into 4 groups (n=6 in each group), namely group A (normoxia and common diet), group B (normoxia and high fat diet), Group C (CIH and common diet), and group D (CIH and high fat diet). The serum cystatin C (Cys-C) was measured and the renal CHOP protein was detected by immunohistochemistry. The ultrastructural changes of glomeruli and renal tubules were observed under electron microscope. Results The levels of Cys-C in group B, group C and group D were significantly higher than those in group A (P<0.05). The mean density of endoplasmic reticulum stress (ERS) marker protein CHOP in group B, group C and group D was significantly higher than that in group A (P<0.05). Electron microscope revealed focal nuclear pyknosis in the partly renal tubular epithelial cells, sparse and scattered brush border in group B and group C, also revealed nuclear pyknosis in a large number of tubular epithelial cells, sparse and scattered brush border in group D. Conclusion CIH can activate the ERS mediated renal tubular epithelial apoptosis, thus induce ultrastructure changes and damage of kidney.
Objective To explore the difference between the hemorheology levels and the expression of hypoxia inducible factor 1α/2α (HIF-1α/2α) in the peripheral blood mononuclear cells of the Tibetan and Han patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods This research recruited 30 high-risk Tibetan and Han patients with OSAHS, and 30 Tibetan and Han healthy volunteers at the same period. The whole blood viscometer was used to detect the high shear rate of whole blood viscosity, low shear rate of whole blood viscosity, plasma viscosity ratio, red blood cell aggregation index, and hematocrit in each group. RT-qPCR and Western blot assays were used to detect the mRNA and protein levels of phosphoinositide 3-kinase (PI3K), serine/threonine kinase (AKT), nuclear factor-κB (NF-κB) p65, HIF-1α and HIF-2α in peripheral blood mononuclear cells. Results The hemorheology level of Tibetan OSAHS patients was significantly higher than that of healthy Tibetans and Han OSAHS patients (P<0.05), and the hemorheology level of Han OSAHS patients was significantly higher than that of Han healthy people (P<0.05) . The mRNA and protein levels of PI3K, AKT, NF-κB p65 and HIF-1α in the peripheral blood mononuclear cells of Tibetan OSAHS patients were significantly higher than those of the healthy Tibetans or Han people, and these indexes of the Han OSAHS patients were significantly higher than those of the Han healthy people (all P<0.05), while HIF-2α mRNA and protein levels were significantly lower than those of healthy Han people (all P<0.05). Conclusion The upregulation of HIF-1α level and downregulation of HIF-2α expression in peripheral blood mononuclear cells of OSAHS patients depend on the activation of the PI3K/AKT/NF-κB p65 signaling pathway, and the hemorheological level of Tibetan OSAHS patients is higher than that of Han OSAHS patients.
Objective To investigate the possible association between serum level of hepatocyte growth factor( HGF) and obstructive sleep apnea hypopnea syndrome( OSAHS) with hypertension.Methods 58 cases of OSAHS without hypertension, 61 cases of OSAHS with hypertension, and 50 normal controls were enrolled. Serum level of HGF was measured by enzyme-linked immunosorbent assay( ELISA) , and the relationships between the serum HGF level and blood pressure( BP) , apnea hypopnea index( AHI) , lowest SaO2 ( LSaO2 ) were analyzed by linear correlation analysis. Results The serum HGF level ( pg/mL) was 761. 46 ±60. 18, 970. 87 ±60. 94, and 487. 34 ±45. 52 in the OSAHS patients without hypertention, OSAHS patients with hypertention, and normal subjects, respectively. Which was significantly higher in the OSAHSpatients than the normal subjects, and highest in the OSAHS patients with hypertension( P lt; 0. 05) . The serum HGF level was positively related to AHI( r = 0. 452, P lt;0. 05) and negatively related to LSaO2 ( r =- 0. 328, P lt;0. 05) in the OSAHS patients without hypertention, positively related to AHI, SBP, DBP( r =0. 670, P lt;0. 01; r =0. 535, P lt;0. 05; r =0. 424, P lt;0. 05) and negatively related to LSaO2 ( r = - 0. 572,P lt;0. 01) in the OSAHS patients with hypertension. Conclusions SerumHGF level increases significantly in patients with OSAHS especialy in OSAHS patients with hypertension, and positively correlates with the severity of OSAHS and hypertension.
ObjectiveTo investigate the expression of C/EBP homologous protein (CHOP) in lung tissue of chronic intermittent hypoxia rats, and explore the intervention effect of edaravone and its possible mechanism.MethodsA total of 120 adult male Wistar rats were randomly divided into three groups: a normal control group (UC group), a chronic intermittent hypoxia group (CIH group), an edaravone intervention group (NE group), and a normal saline group (NS group). The above four groups were also randomly divided into five time subgroups of 3 days, 7 days, 14 days, 21 days and 28 days, respectively, with 6 rats in each time subgroup. The histopathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining and the expression of CHOP in lung tissue was detected by immunohistochemical method.ResultsHE staining results showed that there was no obvious pathological change in UC group. The epithelial cells of lung tissue in CIH group showed edema, hyperemia, widening of alveolar septum and inflammatory cell infiltration. The pathological injury was more serious with the prolongation of intermittent hypoxia time. There were also pathological changes in NE group, but the degree of lung tissue injury was significantly lower than that in CIH group. The results of immunohistochemistry showed that the expression of CHOP in CIH group was significantly higher than that in UC group. The expression of CHOP in NE group was higher than that in UC group, but it was still significantly lower than that in CIH group.ConclusionsThe expression of CHOP protein in lung tissue of chronic intermittent hypoxic rats is enhanced and the high expression of CHOP protein plays a certain role in the lung injury of chronic intermittent hypoxia rats complicated with lung injury. Edaravone may protect lung tissue from chronic intermittent hypoxia by inhibiting the expression of CHOP.
Objective To explore the relationship between obstructive sleep apnea hypopnea syndrome ( OSAHS) and airway hyperresponsiveness ( AHR) . Methods 197 subjects suspected for OSAHS were enrolled in the study. They were all performed overnight polysomnogram ( PSG) monitoring and lung function test. Acoording to the results of FEV1% pred, they were performed bronchial provocation test( BPT)or brochial dilation test( BDT) . The relation between apnea hypopnea index ( AHI) and the degree of airway hyperresponsiveness ( AHR, expressed as PD20 -FEV1 ) was evaluated by linear correlation analysis. Results 117 patients were diagnosed as OSAHS, in which 28 cases were complicated with AHR( 3 cases with positive BDT result, 25 cases with AHR) . In 80 non-OSAHS patients, 7 cases were complicated with AHR. Theincidence of AHR was higher in the OSAHS patients compared with the non-OSAHS patients( 23. 9% vs 8. 8% , P lt; 0. 01 ) . AHI of OSAHS patients with AHR was higher than OSAHS patients without AHR[ ( 30. 3 ±5. 1) /h vs ( 23. 7 ±2. 4) /h, P lt;0. 01] . There was a positive correlation between AHI and degree of AHR in OSAHS patients with AHR( r=0. 62, P lt;0. 05, n=25) . Conclusion OSAHS is associated with an increased risk of AHR.
Objective To explore the contribution of obstructive sleep apnea hypopnea syndrome(OSAHS) in the variations of blood pressure in the evening to morning and possible mechanisms.Methods In Sleep and Breathing Disorders Centre，from September 2003 to September 2007，adult patients whose Epworth sleeping scoregt;9 were undergone polysomnography(PSG) and divided into 4 groups according to apnea hyponea index(AHI).The levels of blood pressure were monitored and compared between evening and morning.Correlations between PSG indexes and variations of the systolic blood pressure(SBP) and diastolic blood pressure(DBP) were analyzed in OSAHS patients.Results 1 528 patients were enrolled in this study.There was no significant difference between the evening and morning blood pressure in the non-OSAHS group(AHIlt;5，n=172)，whereas DBP rised about 1.73 mm Hg in the mild OSAHS group(AHI≤20，n=435)，SBP and DBP rised about 3.52 and 3.71 mm Hg respectively in the moderate OSAHS group(AHI≤40，n=307)，and SBP and DBP rised about 3.72 and 4.22 mm Hg respectively in the severe OSAHS group(AHIgt;40，n=614).The variation of SBP during the night correlated positively with the arousal index in the mild OSAHS group（r=0.25，Plt;0.05），but with the body mass index (BMI) in the moderate OSAHS group（r=0.25，Plt;0.05）.In the severe OSAHS group，the variation of SBP during the night correlated positively with BMI and the longest apnea time (LA)（r=0.26，0.25，both Plt;0.05），the variation of DBP during the night correlated positively with AHI and mean apnea duration(MA)（r=0.22，0.17，both Plt;0.05），and the variation of mean arterial pressure during the night correlated positively with AHI and MA（r=0.25，0.20，both Plt;0.05）.Conclusion OSAHS may induce mild rises of the blood pressure at night.The relevant factors that influence the blood pressure are different in different severity of the OSAHS.
ObjectiveTo systematically review the association between the level of plasma YKL-40 and obstructive sleep apnea hypopnea syndrome (OSAHS).MethodsWe searched PubMed, EMbase, MEDLINE, CNKI, WanFang Data, VIP database and supplemented by Google academic retrieval to collect case-control studies about the association between the level of plasma YKL-40 and OSAHS from inception to April 2017. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of included studies. And then, meta-analysis was performed by RevMan 5.3 software.ResultsA total of 5 case-control studies were included, involving 755 OSAHS patients and control population. The results of meta-analysis showed that the level of plasma YKL-40 in OSAHS patients was higher than that in control group (SMD=1.20, 95%CI 0.33 to 2.06, P=0.007). The subgroup analysis showed that the level of plasma YKL-40 in OSAHS patients from Asia was significantly higher than that in control group (SMD=1.79, 95%CI 0.83 to 2.75, P=0.000 2). The comparison between different severity of OSAHS showed that the wild-medium group had lower plasma level of YKL-40 than the severe group (SMD=–0.83, 95%CI –1.46 to –0.19, P=0.01).ConclusionYKL-40 may play an important role in the pathogenesis of OSAHS. Due to limited quantity and quality of the included studies, more high quality studies are needed to verify above conclusions.
ObjectiveTo investigate the effects and clinical significance of edaravone on serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) in elderly patients with obstructive sleep apnea hypopnea syndrome (OSAHS).MethodsA total of 90 elderly patients with moderate to severe OSAHS confirmed by polysomnography were recruited from North China University of Science and Technology Affiliated Hospital in February 2016 to October 2017. According to random number table method the OSAHS patients were randomly divided into group A (n=30), group B (n=30) and group C (n=30). Group A received continuous positive airway pressure treatment for six months, group B received edaravone therapy and continuous positive airway pressure treatment for six months, and group C only received edaravone therapy for six months. The changes of serum TNF-α, IL-6 and ICAM-1 were detected by enzyme-linked immunosorbent assay before and after treatment.ResultsThe differences of serum TNF-α, IL-6 and ICAM-1 before treatment in the three groups were not statistically significant (P>0.05). Compared with before treatment, the levels of serum TNF-α, IL-6 and ICAM-1 decreased in the three groups (P<0.05). After six months of treatment, the levels of serum TNF-α, IL-6 and ICAM-1 decreased in group A and group B compared with group C (P<0.05), and decreased significantly in group B compared with group A (P<0.05).ConclusionEdaravone can inhibit the expressions of serum TNF-α, IL-6 and ICAM-1 in elderly patients with moderate to severe OSAHS, and thereby reduce vascular endothelial dysfunction and injury.
ObjectiveTo assess the fatigue in patients with obstructive sleep apnea hypopnea syndrome (OSAHS), and analyze the factors caused fatigue and the relationship between quality of life (QOL) and fatigue. MethodsOne hundred and sixty-nine patients with OSAHS and 78 subjects without OSAHS diagnosed by polysomnography (PSG) between December 2010 and March 2011 in West China Hospital were recruited in the study. Fatigue was assessed by using multidimensional fatigue inventory (MFI), excessive daytime sleepiness by Epworth sleepiness scale(ESS), QOL by functional outcomes of sleep questionnaire (FOSQ). ResultsFatigue in the patients with OSAHS was more severe than that of the controls (51.06±13.39 vs. 44.82±9.81, P < 0.001), but no difference was revealed in the patients with different degree of OSAHS. Fatigue was positively correlated with ESS score(r=0.210), total sleep time intervals(r=0.156), and the ratio of time of SpO2 below 90% in total sleep time(r=0.153)(P < 0.05), and was negatively correlated with the average oxygen saturation(r=-0.171, P < 0.05) and all subscales of FOSQ(P < 0.01). ConclusionsFatigue in patients with OSAHS is more severe than that of controls. Fatigue can significantly reduce QOL, and the impact is greater than that of excessive daytime sleepiness.
ObjectiveTo explore the mechanism of renal tubular epithelial cell apoptosis induced by endoplasmic reticulum stress in rats with intermittent hypoxia (IH) and the intervention effect of losartan.MethodsSixty SPF grade healthy male SD rats were randomly divided into four groups (15 rats in each group), namely as group A (control group), group B (IH group), group C (IH+losartan group), and group D (IH+saline group). The group C and D were intraperitoneally injected with losartan 30 mg/kg and the same dose of saline 30 minutes daily before the experiment, and then the group B, C and D were placed in the intermittent hypoxia chamber. After 6 weeks of modeling, serum of the rats was sampled to detect the renal function. Hematoxylin-eosin staining was used to observe histomorphological changes of the kidney; transmission electron microscopy was used to observe ultrastructural changes of the kidney; TUNEL was used to detect apoptotic index of the renal tubular epithelial cells; and RT-PCR method was used to detect expressions of caspase-12, JNK and CHOP mRNA in the kidney.ResultsThe differences of renal function among these four groups were statistically significant (all P<0.05). Hematoxylin-eosin staining and transmission electron microscopy showed the histomorphological and ultrastructural changes of the kidneys in group B, C and D compared with group A, and the damages in group B and D were more significant. TUNEL results showed that the apoptotic index of renal tubular epithelial cells in group B and D was significantly higher than that in group A (P<0.01), while that in group C was significantly lower than that in group B and D (all P<0.01). RT-PCR results showed that caspase-12, JNK and CHOP mRNA expressions were significantly higher in group B and D than those in group A (all P<0.01); caspase-12 mRNA expression was significantly lower in group C than that in group B and D (P<0.01; P<0.05); and CHOP mRNA expression was significantly lower in group C than that in group B and D (all P<0.01).ConclusionsIH may induce apoptosis of renal tubular epithelial cells by activating endoplasmic reticulum stress through caspase-12, JNK and CHOP. Losartan has protective effects on the kidney of rats with intermittent hypoxia. Its mechanism may be related to the inhibition of apoptotic pathways mediated by endoplasmic reticulum stress.