Background Obstructive sleep apnea syndrome （OSAS） is an important risk factor for cardiovascular diseases. Chronic intermittent hypoxia （CIH） is considered to be one of the most important causes of cardiovascular...Background Obstructive sleep apnea syndrome （OSAS） is an important risk factor for cardiovascular diseases. Chronic intermittent hypoxia （CIH） is considered to be one of the most important causes of cardiovascular diseases in OSA patients. This repeated hypoxia and reoxygenation cycle is similar to hypoxia-reperfusion injury, which initiates oxidative stress. In this study, we observed cardiocytes injury induced by CIH and the effect of N-acetylcysteine （NAC）. Methods Thirty ICR mice were randomly assigned to 3 groups： control, CIH and NAC （CIH＋NAC） groups. Malondialdehyde （MDA） and superoxide dismutase （SOD） of cardiocyte homogenates were measured. Serum lipids were measured by an instrument method. Serum cardiac troponin I （cTnl） was detected by enzyme-linked immunosorbent assays （ELISA）. Myocardium pathological sections were observed. Results （1） The SOD activity and MDA concentration of cardiocyte homogenates in the CIH group were significantly higher than in other groups （P 〈0.005）. The MDA concentration of the NAC group was lower than that of the control group （P 〈0.01）. （2） The serum cTnl concentration of the CIH and NAC groups was significantly higher than that of the control group （P 〈0.01）. （3） Serum triglyceride levels in the NAC group were lower than in the other groups （P 〈0.01）, while there were no significant differences in low density lipoprotein and high density lipoprotein among the three groups. （4） The degeneration of myocardium, transverse striation blurred, and fabric effusion were observed in tissue sections in the CIH and NAC groups. However, normal tissue was found in the control group. Conclusion The oxidative stress induced by CIH can injure cardiocytes and the injury effect can be partially inhibited by NAC.展开更多
Obstructive sleep apnea syndrome （OSAS） and hypertension commonly coexist. Clinical studies indicate that OSAS plays a key role in increasing the risk of prevalent hypertension. Chronic intermittent hypoxia （CIH） ...Obstructive sleep apnea syndrome （OSAS） and hypertension commonly coexist. Clinical studies indicate that OSAS plays a key role in increasing the risk of prevalent hypertension. Chronic intermittent hypoxia （CIH） is the core pathological mechanism of OSAS, and has a close relationship with systemic inflammation. Growing evidence shows that CIH and hypertension are strongly related, involving markers or pathways indicative of systemic inflammation, such as high-sensitivity C-reactive protein （hs-CRP）, interteukin-6, nuclear factor-kappa B, tumor necrosis factor-α, interleukin-8 and p38 mitogen-activated protein kinase （MAPK）dependent pathways. Oxidative stress also plays an important role in this process, including in the activation of polymorphonuclear neutrophils. However, the pathophysiological and clinical significance of systemic inflammation in CIH and hypertension is not proven. This review article highlights the relationship between CIH and hypertension through systemic inflammation and the current interventions available in Chinese medicine, to offer a background for the future treatment of OSAS-related hypertension with integrative medicine.展开更多
Background： Cognitive impairment is a severe complication caused by obstructive sleep apnea （OSA）. The mechanisms of causation are still unclear. The Wntβ-catenin signaling pathway is involved in cognition, and ab...Background： Cognitive impairment is a severe complication caused by obstructive sleep apnea （OSA）. The mechanisms of causation are still unclear. The Wntβ-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wntβ-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia （CIH）, the most characteristic pathophysiological component of OSA. Methods： We divided 32 4-week-old male C57/BL mice into four groups of eight each： a CIH ＋ normal saline （NS） group, CIH ＋ LiCI group, sham CIH ＋ NS group, and a sham CIH ＋ LiCI group. The spatial learning performance of each group was assessed by using the Morris water maze （MWM）. Protein expressions of glycogen synthase kinase-β （GSK-β） and β-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region. Results： Mice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-313 activity increased, and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCI decreased the activity of GSK-β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH. Conclusions： Wntβ-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCI might attenuate CIH-induced cognitive impairment via Wntβ-c展开更多
Yi-Qi-Fu-Mai(YQFM) is extensively used clinically to treat cardiovascular diseases in China. To explore the anti-hypoxia effect of the extract of YQFM preparation(EYQFM), the EYQFM(1.4, 2.8, and 5.5 g·kg-1·d...Yi-Qi-Fu-Mai(YQFM) is extensively used clinically to treat cardiovascular diseases in China. To explore the anti-hypoxia effect of the extract of YQFM preparation(EYQFM), the EYQFM(1.4, 2.8, and 5.5 g·kg-1·d-1) was assessed for its heart-protective effect in a chronic intermittent hypoxia(CIH) animal model(oxygen pressure 7%-8%, 20 min per day) for 28 days of treatment. Betaloc(0.151 6 g·kg^(-1)·d^(-1)) was used as a positive control. The histopathological analyses of heart in CIH mice were conducted. Several cardiac state parameters, such as left ventricular ejection fractions(EF), stroke volume(SV), expression of creatine kinase(CK), lactate dehydrogenase(LDH), superoxide dismutase(SOD), and malondialdehyde(MDA) were measured. The results showed that treatment with EYQFM markedly reversed swelling of the endothelial cells and vacuolization in the heart when compared with the model group. Further study demonstrated that EYQFM significantly improved ventricular myocardial contractility by increasing EF and SV. In addition, EYQFM inhibited the activity of CK, LDH, decreased the level of MDA and improved SOD activity. The results demonstrated that EYQFM significantly improved the tolerability of myocardium to hypoxia and ameliorated the cardiac damage in the CIH model.展开更多
Background The prevalence of obstructive sleep apnea （OSA） increases after menopause in women, but remains under diagnosed because of social or lifestyle factors. It is important to evaluate the hazards of OSA on ca...Background The prevalence of obstructive sleep apnea （OSA） increases after menopause in women, but remains under diagnosed because of social or lifestyle factors. It is important to evaluate the hazards of OSA on cardiovascular disease in menopausal women. We tested the hypothesis that chronic intermittent hypoxia （CIH） may aggravate cardiomyocyte apoptosis in ovariectomized （OVX） Sprague Dawley （SD） rats; the changes of anti-oxidation ability in cardiac muscles may be one of the reasons for cardiomyocyte apoptosis. Methods Forty-eight 60-day old female SD rats were randomly divided into a CIH group, OVX group, OVX±CIH （OC） group, and handled control （HC） group, and the rats were exposed either to CIH （nadir 02 6%） or handled normoxic controls. The changes of body weight and whole heart weight were measured. Super oxide dismutase （SOD） and malonaldehyde （MDA） were used to evaluate the level of oxidative stress. TdT-mediated dUTP nick end labeling （TUNEL） was used to measure apoptosis in each rat. Western blotting was used to measure apoptosis associated proteins in cardiac muscle samples from each rat. Results When compared with the HC and CIH groups, the levels of oxidative stress in the OC and OVX groups were significantly higher. The levels of SOD in the HC, CIH, OC, and OVX groups were （47.99±4.89）, （53.60±4.47）, （20.99±2.72）, and （30.64±3.79） mmol/mg protein; significantly increased in the CIH group （P 〈0.05） and significantly decreased in the OC （P 〈0.01） and OVX （P 〈0.05） groups. The levels of MDA in the HC, CIH, OVX, and OC groups were （1.63±0.20）, （1.93±0.77）, （3.30±0.39）, and （1.95_±0.20） mmol/mg protein; it significantly increased in the CIH （P 〈0.05）, OC （P 〈0.01）, and OVX （P 〈0.05） groups compared with the HC group. Bax protein expression was significantly increased and bcl-2 protein expression was significantly reduced after CIH compared with HC rats （P 〈0.05）. The protein expre展开更多
Objective: To discuss the expression of RUNX2 and MDM21 in rats with periodontitis under the chronic intermittent hypoxia. Methods: A total of 32 SD healthy rats were randomly divided into four groups, with 8 rats in ...Objective: To discuss the expression of RUNX2 and MDM21 in rats with periodontitis under the chronic intermittent hypoxia. Methods: A total of 32 SD healthy rats were randomly divided into four groups, with 8 rats in each group. The molecular biological techniques of immunohistochemistry, RT-PCR and Western blotting were employed to detect the effect of different hypoxia time(0, 6, 12, 24 and 48 h) and different concentrations of hypoxia(0.000, 0.001, 0.010, 0.060 and 0.100 ppm) on the expression of RUNX2 and MDM21 in rats of four groups. Results: The expression of RUNX2 and MDM21 in each group was significantly higher than the one at other concentrations when the concentration was 0.010 ppm, with the statistical difference(P<0.05). The expression of RUNX2 and MDM21 was that normoxic control group > periodontitis group> chronic intermittent hypoxia group > compound group under the action with the concentration of 0.010 ppm for 12 h, but there was no significant difference for the comparison among groups(P>0.05). Conclusions: The condition of chronic intermittent hypoxia can reduce the expression of RUNX2 and MDM21 in rats with periodontitis and aggravate the damage of periodontal bone.展开更多
基金This study was supported by the grants from National Natural Science Foundation of China （No. 30770954） and the Nanjing Technology Plan Projects （No. 20080253） and Jiangsu Province College Students Practical Innovative Training Plan Projects （No. 2007012）.
文摘Background Obstructive sleep apnea syndrome （OSAS） is an important risk factor for cardiovascular diseases. Chronic intermittent hypoxia （CIH） is considered to be one of the most important causes of cardiovascular diseases in OSA patients. This repeated hypoxia and reoxygenation cycle is similar to hypoxia-reperfusion injury, which initiates oxidative stress. In this study, we observed cardiocytes injury induced by CIH and the effect of N-acetylcysteine （NAC）. Methods Thirty ICR mice were randomly assigned to 3 groups： control, CIH and NAC （CIH＋NAC） groups. Malondialdehyde （MDA） and superoxide dismutase （SOD） of cardiocyte homogenates were measured. Serum lipids were measured by an instrument method. Serum cardiac troponin I （cTnl） was detected by enzyme-linked immunosorbent assays （ELISA）. Myocardium pathological sections were observed. Results （1） The SOD activity and MDA concentration of cardiocyte homogenates in the CIH group were significantly higher than in other groups （P 〈0.005）. The MDA concentration of the NAC group was lower than that of the control group （P 〈0.01）. （2） The serum cTnl concentration of the CIH and NAC groups was significantly higher than that of the control group （P 〈0.01）. （3） Serum triglyceride levels in the NAC group were lower than in the other groups （P 〈0.01）, while there were no significant differences in low density lipoprotein and high density lipoprotein among the three groups. （4） The degeneration of myocardium, transverse striation blurred, and fabric effusion were observed in tissue sections in the CIH and NAC groups. However, normal tissue was found in the control group. Conclusion The oxidative stress induced by CIH can injure cardiocytes and the injury effect can be partially inhibited by NAC.
基金Supported by the Special Research Foundation of National Clinical Research Facility of Traditional Chinese Medicine (No.JDZX2012108)China Postdoctoral Foundation(No. 200902187)+1 种基金Famous Doctor Inheritance Research Foundation of China Academy of Chinese Medical Sciences(CM20121018) "3+3" Famous Doctor Inheritance Program of Beijing Administration of Traditional Chinese Medicine
文摘Obstructive sleep apnea syndrome （OSAS） and hypertension commonly coexist. Clinical studies indicate that OSAS plays a key role in increasing the risk of prevalent hypertension. Chronic intermittent hypoxia （CIH） is the core pathological mechanism of OSAS, and has a close relationship with systemic inflammation. Growing evidence shows that CIH and hypertension are strongly related, involving markers or pathways indicative of systemic inflammation, such as high-sensitivity C-reactive protein （hs-CRP）, interteukin-6, nuclear factor-kappa B, tumor necrosis factor-α, interleukin-8 and p38 mitogen-activated protein kinase （MAPK）dependent pathways. Oxidative stress also plays an important role in this process, including in the activation of polymorphonuclear neutrophils. However, the pathophysiological and clinical significance of systemic inflammation in CIH and hypertension is not proven. This review article highlights the relationship between CIH and hypertension through systemic inflammation and the current interventions available in Chinese medicine, to offer a background for the future treatment of OSAS-related hypertension with integrative medicine.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81370185）.
文摘Background： Cognitive impairment is a severe complication caused by obstructive sleep apnea （OSA）. The mechanisms of causation are still unclear. The Wntβ-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wntβ-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia （CIH）, the most characteristic pathophysiological component of OSA. Methods： We divided 32 4-week-old male C57/BL mice into four groups of eight each： a CIH ＋ normal saline （NS） group, CIH ＋ LiCI group, sham CIH ＋ NS group, and a sham CIH ＋ LiCI group. The spatial learning performance of each group was assessed by using the Morris water maze （MWM）. Protein expressions of glycogen synthase kinase-β （GSK-β） and β-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region. Results： Mice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-313 activity increased, and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCI decreased the activity of GSK-β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH. Conclusions： Wntβ-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCI might attenuate CIH-induced cognitive impairment via Wntβ-c
基金supported by the National Natural Science Foundations of China(Nos.81274004,81473317)
文摘Yi-Qi-Fu-Mai(YQFM) is extensively used clinically to treat cardiovascular diseases in China. To explore the anti-hypoxia effect of the extract of YQFM preparation(EYQFM), the EYQFM(1.4, 2.8, and 5.5 g·kg-1·d-1) was assessed for its heart-protective effect in a chronic intermittent hypoxia(CIH) animal model(oxygen pressure 7%-8%, 20 min per day) for 28 days of treatment. Betaloc(0.151 6 g·kg^(-1)·d^(-1)) was used as a positive control. The histopathological analyses of heart in CIH mice were conducted. Several cardiac state parameters, such as left ventricular ejection fractions(EF), stroke volume(SV), expression of creatine kinase(CK), lactate dehydrogenase(LDH), superoxide dismutase(SOD), and malondialdehyde(MDA) were measured. The results showed that treatment with EYQFM markedly reversed swelling of the endothelial cells and vacuolization in the heart when compared with the model group. Further study demonstrated that EYQFM significantly improved ventricular myocardial contractility by increasing EF and SV. In addition, EYQFM inhibited the activity of CK, LDH, decreased the level of MDA and improved SOD activity. The results demonstrated that EYQFM significantly improved the tolerability of myocardium to hypoxia and ameliorated the cardiac damage in the CIH model.
文摘Background The prevalence of obstructive sleep apnea （OSA） increases after menopause in women, but remains under diagnosed because of social or lifestyle factors. It is important to evaluate the hazards of OSA on cardiovascular disease in menopausal women. We tested the hypothesis that chronic intermittent hypoxia （CIH） may aggravate cardiomyocyte apoptosis in ovariectomized （OVX） Sprague Dawley （SD） rats; the changes of anti-oxidation ability in cardiac muscles may be one of the reasons for cardiomyocyte apoptosis. Methods Forty-eight 60-day old female SD rats were randomly divided into a CIH group, OVX group, OVX±CIH （OC） group, and handled control （HC） group, and the rats were exposed either to CIH （nadir 02 6%） or handled normoxic controls. The changes of body weight and whole heart weight were measured. Super oxide dismutase （SOD） and malonaldehyde （MDA） were used to evaluate the level of oxidative stress. TdT-mediated dUTP nick end labeling （TUNEL） was used to measure apoptosis in each rat. Western blotting was used to measure apoptosis associated proteins in cardiac muscle samples from each rat. Results When compared with the HC and CIH groups, the levels of oxidative stress in the OC and OVX groups were significantly higher. The levels of SOD in the HC, CIH, OC, and OVX groups were （47.99±4.89）, （53.60±4.47）, （20.99±2.72）, and （30.64±3.79） mmol/mg protein; significantly increased in the CIH group （P 〈0.05） and significantly decreased in the OC （P 〈0.01） and OVX （P 〈0.05） groups. The levels of MDA in the HC, CIH, OVX, and OC groups were （1.63±0.20）, （1.93±0.77）, （3.30±0.39）, and （1.95_±0.20） mmol/mg protein; it significantly increased in the CIH （P 〈0.05）, OC （P 〈0.01）, and OVX （P 〈0.05） groups compared with the HC group. Bax protein expression was significantly increased and bcl-2 protein expression was significantly reduced after CIH compared with HC rats （P 〈0.05）. The protein expre
基金supported by Natural Science Research Program of Henan Education Department(No.201302X63)
文摘Objective: To discuss the expression of RUNX2 and MDM21 in rats with periodontitis under the chronic intermittent hypoxia. Methods: A total of 32 SD healthy rats were randomly divided into four groups, with 8 rats in each group. The molecular biological techniques of immunohistochemistry, RT-PCR and Western blotting were employed to detect the effect of different hypoxia time(0, 6, 12, 24 and 48 h) and different concentrations of hypoxia(0.000, 0.001, 0.010, 0.060 and 0.100 ppm) on the expression of RUNX2 and MDM21 in rats of four groups. Results: The expression of RUNX2 and MDM21 in each group was significantly higher than the one at other concentrations when the concentration was 0.010 ppm, with the statistical difference(P<0.05). The expression of RUNX2 and MDM21 was that normoxic control group > periodontitis group> chronic intermittent hypoxia group > compound group under the action with the concentration of 0.010 ppm for 12 h, but there was no significant difference for the comparison among groups(P>0.05). Conclusions: The condition of chronic intermittent hypoxia can reduce the expression of RUNX2 and MDM21 in rats with periodontitis and aggravate the damage of periodontal bone.
