Muscle-specific overexpression of Atg2 gene and endurance exercise delay age-related deteriorations of skeletal muscle and heart function via activating the AMPK/Sirt1/PGC-1α pathway in male Drosophila.

Atg2 is a key gene in autophagy formation and plays an important role in regulating aging progress. Exercise is an important tool to resist oxidative stress in cells and delay muscle aging. However, the relationship between exercise and the muscle Atg2 gene in regulating skeletal muscle aging remains unclear. Here, overexpression or knockdown of muscle Atg2 gene was achieved by constructing the AtgUAS/MhcGal4 system in Drosophila, and these flies were also subjected to an exercise intervention for 2 weeks. The results showed that both overexpression of Atg2 and exercise significantly increased the climbing speed, climbing endurance, cardiac function, and lifespan of aging flies. They also significantly up-regulated the expression of muscle Atg2, AMPK, Sirt1, and PGC-1α genes, and they significantly reduced muscle malondialdehyde and triglyceride. These positive benefits were even more pronounced when the two were combined. However, the effects of Atg2 knockdown on skeletal muscle, heart, and lifespan were reversed compared to its overexpression. Importantly, exercise ameliorated age-related changes induced by Atg2 knockdown. Therefore, current results confirmed that both overexpression of muscle Atg2 and exercise delayed age-related deteriorations of skeletal muscle, the heart function, and lifespan, and exercise could also reverse age-related changes induced by Atg2 knockdown. The molecular mechanism is related to the overexpression of the Atg2 gene and exercise, which increase the activity of the AMPK/Sirt1/PGC-1α pathway, oxidation and antioxidant balance, and lipid metabolism in aging muscle.

Risk factors for familial clustering of hepatitis C virus infection in a Chinese Han population: a cross-sectional study.

BACKGROUND: Hepatitis C is a curable disease, but reinfection from household contact may occur in patients who have achieved sustained viral response (SVR). METHODS: A total of 997 ethnic Han HCV treatment-naïve adult patients were enrolled in a cross-sectional study with stratified sampling based on the populations of five geographic regions across China to examine the genetic and physiological parameters associated with the phenomenon of HCV familial clustering. RESULTS: Of the total 997 patients, there were 59 patients who had at least one family member with HCV infection according to patient self-report. Comparison between patients with and without HCV familial clustering by univariate regression analysis showed that genotype 2, sexual transmission, long-term exposure to HCV patients, monthly family income per person less than 2000 yuan, farming occupation, and the southern and northern regions were associated with HCV familial clustering. Blood transfusion was negatively associated with HCV familial clustering. Multivariate logistic regression analysis suggested that long-term exposure to HCV patients and low family income were correlated with HCV familial clustering, whereas blood transfusion was negatively associated, which meant that blood transfusion was not the main transmission route in HCV familial clustering. CONCLUSION: Long-term exposure to HCV patients and low family income were correlated with HCV familial clustering, whereas blood transfusion was not the main transmission route in HCV familial clustering. To reduce reinfection from household contacts, education and awareness of HCV transmission routes and familial clustering should be strengthened, especially among HCV patients' family members, low-income families and non-blood transmission hepatitis C patients.

Muscle Psn gene combined with exercise contribute to healthy aging of skeletal muscle and lifespan by adaptively regulating Sirt1/PGC-1α and arm pathway.

The Presenilin (Psn) gene is closely related to aging, but it is still unclear the role of Psn genes in skeletal muscle. Here, the Psn-UAS/Mhc-GAL4 system in Drosophila was used to regulate muscle Psn overexpression(MPO) and muscle Psn knockdown(MPK). Drosophila were subjected to endurance exercise from 4 weeks to 5 weeks old. The results showed that MPO and exercise significantly increased climbing speed, climbing endurance, lifespan, muscle SOD activity, Psn expression, Sirt1 expression, PGC-1α expression, and armadillo (arm) expression in aged Drosophila, and they significantly decreased muscle malondialdehyde levels. Interestingly, when the Psn gene is knockdown by 0.78 times, the PGC-1α expression and arm expression were also down-regulated, but the exercise capacity and lifespan were increased. Furthermore, exercise combined with MPO further improved the exercise capacity and lifespan. MPK combined with exercise further improves the exercise capacity and lifespan. Thus, current results confirmed that the muscle Psn gene was a vital gene that contributed to the healthy aging of skeletal muscle since whether it was overexpressed or knocked down, the aging progress of skeletal muscle structure and function was slowed down by regulating the activity homeostasis of Sirt1/PGC-1α pathway and Psn/arm pathway. Exercise enhanced the function of the Psn gene to delay skeletal muscle aging by up regulating the activity of the Sirt1/PGC-1α pathway and Psn/arm pathway.

Role of muscle FOXO gene in exercise against the skeletal muscle and cardiac age-related defects and mortality caused by high-salt intake in Drosophila.

FOXO has long been associated with aging, exercise, and tissue homeostasis, but it remains unclear what the role is of the muscle FOXO gene in E against high-salt intake(HSI)-induced age-related defects of the skeletal muscle, heart, and mortality. In this research, overexpression and RNAi of the FOXO gene in the skeletal and heart muscle of Drosophila were constructed by building Mhc-GAL4/FOXO-UAS-overexpression and Mhc-GAL4/FOXO-UAS-RNAi system. The skeletal muscle and heart function, the balance of oxidation and antioxidant, and mitochondrial homeostasis were measured. The results showed that exercise reversed the age-related decline in climbing ability and downregulation of muscle FOXO expression induced by HSI. Muscle-specific FOXO-RNAi (FOXO-RNAi) and -overexpression (FOXO-OE) promoted or slowed the age-related decline in climbing ability, heart function, and skeletal muscle and heart structure damage, which was accompanied by the inhibition or activation of FOXO/PGC-1α/SDH and FOXO/SOD pathway activity, and oxidative stress (ROS) increased or decreased in both skeletal muscle and heart. The protective effect of exercise on the skeletal muscle and heart was blocked by FOXO-RNAi in aged HSI flies. FOXO-OE prolonged its lifespan, but it did not resist the HSI-induced lifespan shortening. Exercise did not improve HSI-induced lifespan shortening in FOXO-RNAi flies. Therefore, current results confirmed that the muscle FOXO gene played a vital role in exercise against age-related defects of the skeletal muscle and heart induced by HSI because it determined the activity of muscle FOXO/SOD and FOXO/PGC-1α/SDH pathways. The muscle FOXO gene also played an important role in exercise against HSI-induced mortality in aging flies.

[Clinical features of respiratory failure and heart failure in patients with sleep disordered breathing].

OBJECTIVE: To assess the clinical characteristics of heart failure and respiratory failure in patients with sleep disordered breathing (SDB). METHODS: Symptoms, signs, laboratory tests, clinical courses, blood gases responses to voluntary hyperventilation test and non-invasive ventilation treatment were analyzed in 29 patients with SDB. All patients were diagnosed as right and left heart failure and respiratory failure from 1994 to 2009 in Peking University People's Hospital. RESULTS: Among the 29 patients recruited, 13 were male and 16 female. The mean age was 62 ± 13 yrs, and BMI was (34 ± 4) kg/m(2). Fourteen (48.3%) were diagnosed as obstructive sleep apnea syndrome at first visit. Chief complains includes dyspnea, edema, cough, snoring, hypersomnolence, oliguria, and altered mental status. Common signs include obesity, narrow upper airway, cyanosis, moist rales at the base of lungs, enlarged border of cardiac dullness, edema. Polycythemia was seen in 13 patients (44.80%), among the 26 patients who had underwent pulmonary function tests, 14 had FEV(1)/FVC ≥ 70%, the others were FEV(1)/FVC < 70%, with 6 patients had 50% predict value ≤ FEV(1) < 80% predict value and 6 patients had 30% predict value ≤ FEV(1) < 50% predict value. After positive airway pressure (BiPAP and CPAP) treatment, symptoms and arterial blood gases test results improved. Chest X-ray, CT scan and UCG show pulmonary vascular congestion and edema with cardiomegaly and possible pleural effusion, pulmonary hypertension, left ventricular diastolic dysfunction. Five patients underwent 24 h blood pressure monitoring showed non-dipping pattern or morning risen pattern of BP. In 11 patients who undertaken the test, voluntary hyperventilation induced significant improvement of SpO(2), PaCO(2) and PaO(2), and most of the parameters returned from type II respiratory failure to normal level. CONCLUSION: The morbidity of SDB remained to be recognized. This cases report indicated that obese patients complaining of severe dyspnea and edema may have respiratory failure and bilateral heart failure secondary to SDB. The respiratory failure can be completely reversed by voluntary hyperventilation, and noninvasive treatments only could achieve good outcomes in most of the patients.

Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid-enhanced magnetic resonance imaging for evaluating fibrosis regression in chronic hepatitis C patients after direct-acting antiviral.

BACKGROUND: Direct acting antiviral (DAA) therapy has enabled hepatitis C virus infection to become curable, while histological changes remain uncontained. Few valid non-invasive methods can be confirmed for use in surveillance. Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) is a liver-specific magnetic resonance imaging (MRI) contrast, related to liver function in the hepatobiliary phase (HBP). Whether Gd-EOB-DTPA-enhanced MRI can be used in the diagnosis and follow up of hepatic fibrosis in patients with chronic hepatitis C (CHC) has not been investigated. AIM: To investigate the diagnostic and follow-up values of Gd-EOB-DTPA-enhanced MRI for hepatic histology in patients with CHC. METHODS: Patients with CHC were invited to undergo Gd-EOB-DTPA-enhanced MRI and liver biopsy before treatment, and those with paired qualified MRI and liver biopsy specimens were included. Transient elastography (TE) and blood tests were also arranged. Patients treated with DAAs who achieved 24-wk sustained virological response (SVR) underwent Gd-EOB-DTPA-enhanced MRI and liver biopsy again. The signal intensity (SI) of the liver and muscle were measured in the unenhanced phase (UEP) (SIUEP-liver, SIUEP-muscle) and HBP (SIHBP-liver, SIHBP-muscle) via MRI. The contrast enhancement index (CEI) was calculated as [(SIHBP-liver/SIHBP-muscle)]/[(SIUEP-liver/SIUEP-muscle)]. Liver stiffness measurement (LSM) was confirmed with TE. Serologic markers, aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4), were also calculated according to blood tests. The grade of inflammation and stage of fibrosis were evaluated with the modified histology activity index (mHAI) and Ishak fibrosis score, respectively. Fibrosis regression was defined as a ≥ 1-point decrease in the Ishak fibrosis score. The correlation between the CEI and liver pathology was evaluated. The diagnostic and follow-up values of the CEI, LSM, and serologic markers were compared. RESULTS: Thirty-nine patients with CHC were enrolled [average age, 42.3 ± 14.4 years; 20/39 (51.3%) male]. Twenty-one enrolled patients had eligible paired Gd-EOB-DTPA-enhanced MRI and liver tissues after achieving SVR. The mHAI median significantly decreased after SVR [baseline 6.0 (4.5-13.5) vs SVR 2.0 (1.5-5.5), Z = 3.322, P = 0.017], but the median stage of fibrosis did not notably change (P > 0.05). Sixty pairs of qualified MRI and liver tissue samples were available for use to analyze the relationship between the CEI and hepatic pathology. The CEI was negatively correlated with the mHAI (r = -0.56, P < 0.001) and Ishak score (r = -0.69, P < 0.001). Further stratified analysis showed that the value of the CEI decreased with the progression of the stage of fibrosis rather than with the grade of necroinflammation. For patients with Ishak score ≥ 5, the areas under receiver operating characteristics curve of the CEI, LSM, APRI, and FIB-4 were approximately at baseline, 0.87-0.93, and after achieving SVR, 0.83-0.91. The CEI cut-off value was stable (baseline 1.58 and SVR 1.59), but those of the APRI (from 1.05 to 0.24), FIB-4 (from 1.78 to 1.28), and LSM (from 10.8 kpa to 7.1 kpa) decreased dramatically. The APRI and FIB-4 cannot be used as diagnostic means for SVR in patients with Ishak score ≥ 3 (P > 0.05). Seven patients achieved fibrosis regression after achieving SVR. In these patients, the CEI median increased (from 1.71 to 1.83, Z = -1.981, P = 0.048) and those of the APRI (from 1.71 to 1.83, Z = -2.878, P = 0.004) and LSM (from 6.6 to 4.8, Z = -2.366, P = 0.018) decreased. However, in patients without fibrosis regression, the medians of the APRI, FIB-4, and LSM also changed significantly (P < 0.05). CONCLUSION: Gd-EOB-DTPA-enhanced MRI has good diagnostic value for staging fibrosis in patients with CHC. It can be used for fibrotic-change monitoring post SVR in patients with CHC treated with DAAs.

Association between Serum Cystatin C levels and long-term cardiovascular outcomes and all-cause mortality in older patients with obstructive sleep apnea.

Background and Aims: To investigate the association between obstructive sleep apnea (OSA) severity and baseline serum cystatin C (Cys-C) concentration and to explore the association between baseline serum Cys-C and long-term cardiovascular outcomes and mortality in older patients with OSA. Methods: Between January 2015 and October 2017, a total of 1107 consecutive eligible older patients (≥60 years) with OSA were included in this multicenter, prospective cohort study, and baseline demographics, clinical characteristics, sleep parameters, and follow-up outcomes were collected. Participants were divided into different groups based on baseline serum Cys-C levels. The primary end point was major adverse cardiovascular events (MACE) and the secondary end point was all-cause mortality. The correlation between OSA severity and baseline serum Cys-C was evaluated by Spearman correlation analysis. Multivariate Cox regression was used to analyze the association between Cys-C and the incidence of MACE and mortality. Results: Participants included 672 men and 435 women, with a median age of 66 (range, 60-96) years. At baseline, apnea-hypopnea index (AHI) (r = 0.128, p < 0.05), oxygen desaturation index (ODI) (r = 0.116, p < 0.05), and the lowest pulse oxygen saturation (LSpO2) (r = -0.097, p < 0.05) were correlated with serum Cys-C concentration. During the median follow-up period of 42 months, 97 patients (8.8%) experienced MACE and 40 patients (3.6%) experienced death. The association between serum Cys-C levels and the risk of MACE and all-cause mortality was slow rising shaped. The multivariable Cox regression analysis showed patients with a serum Cys-C concentration of ≥1.14 mg/L had higher risks of MACE (HR = 5.30, 95% CI: 2.28-12.30, p < 0.05) and all-cause mortality (HR = 9.66, 95% CI: 2.09-44.72, p < 0.05) compared with patients with serum Cys-C of ≤0.81 mg/L in older patients with OSA. The receiver-operating characteristic curve showed baseline serum Cys-C levels exhibited moderately capable of identifying patients with a long-term risk of clinical adverse events (MACE and mortality). Conclusion: OSA severity was positively correlated with serum Cys-C concentration. High levels of Cys-C were independently associated with increased risks of MACE and all-cause mortality in older patients with OSA, suggesting that lowering Cys-C levels should be considered as a therapeutic target, and monitoring serum Cys-C may be beneficial to the favorable prognosis of older patients with OSA.

Histopathology and the predominantly progressive, indeterminate and predominately regressive score in hepatitis C virus patients after direct-acting antivirals therapy.

BACKGROUND: Histological changes after direct-acting antivirals (DAAs) therapy in hepatitis C virus (HCV) patients has not been elucidated. Whether the predominantly progressive, indeterminate and predominately regressive (P-I-R) score, evaluating fibrosis activity in hepatitis B virus patients has predictive value in HCV patients has not been investigated. AIM: To identify histological changes after DAAs therapy and to evaluate the predictive value of the P-I-R score in HCV patients. METHODS: Chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included. Sustained virologic response (SVR) was defined as an undetectable serum HCV RNA level at 24 wk after treatment cessation. The Ishak system and P-I-R score were assessed. Inflammation improvement and fibrosis regression were defined as a ≥ 2-points decrease in the histology activity index (HAI) score and a ≥ 1-point decrease in the Ishak fibrosis score, respectively. Fibrosis progression was defined as a ≥ 1-point increase in the Ishak fibrosis score. Histologic improvement was defined as a ≥ 2-points decrease in the HAI score without worsening of the Ishak fibrosis score after DAAs therapy. The P-I-R score was also assessed. "absolutely reversing or advancing" was defined as the same directionality implied by both change in the Ishak score and posttreatment P-I-R score; and "probably reversing or advancing" was defined as only one parameter showing directionality. RESULTS: Thirty-eight chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included. The mean age of these patients was 40.9 ± 14.6 years and there were 53% (20/38) males. Thirty-four percent (13/38) of patients were cirrhotic. Eighty-two percent (31/38) of patients achieved inflammation improvement. The median HAI score decreased significantly after SVR (pretreatment 7.0 vs posttreatment 2.0, Z = -5.146, P = 0.000). Thirty-seven percent (14/38) of patients achieved fibrosis improvement. The median Ishak score decreased significantly after SVR (pretreatment 4.0 vs posttreatment 3.0, Z = -2.354, P = 0.019). Eighty-two percent (31/38) of patients showed histological improvement. The P-I-R score was evaluated in 61% (23/38) of patients. The progressive group showed lower platelet (P = 0.024) and higher HAI scores (P = 0.070) before treatment. In patients with stable Ishak stage after treatment: Progressive injury was seen in 22% (4/18) of patients, 33% (6/18) were classified as indeterminate and regressive changes were seen in 44% (8/18) of patients who were judged as probably reversing by the Ishak and P-I-R systems. CONCLUSION: Significant improvement of necroinflammation and partial remission of fibrosis in HCV patients occurred shortly after DAAs therapy. The P-I-R score has potential in predicting fibrosis in HCV patients.

Burst expansion, distribution and diversification of MITEs in the silkworm genome.

BACKGROUND: Miniature inverted-repeat transposable elements (MITEs) are widespread in plants and animals. Although silkworm (Bombyx mori) has a large amount of and a variety of transposable elements, the genome-wide information of the silkworm MITEs is unknown. RESULTS: We used structure-based and homology approaches to search for MITEs in the silkworm genome. We identified 17 MITE families with a total of 5785 members, accounting for ~0.4% of the genome. 7 of 17 MITE families are completely novel based on the nucleotide composition of target site duplication (TSD) and/or terminal inverted repeats (TIR). Silkworm MITEs were widely and nonrandom distributed in the genome. One family named BmMITE-2 might experience a recent burst expansion. Network and diversity analyses for each family revealed different diversification patterns of the silkworm MITEs, reflecting the signatures of genome-shocks that silkworm experienced. Most silkworm MITEs preferentially inserted into or near genes and BmMITE-11 that encodes a germline-restricted small RNA might silence its the closest genes in silkworm ovary through a small RNA pathway. CONCLUSIONS: Silkworm harbors 17 MITE families. The silkworm MITEs preferred to reside in or near genes and one MITE might be involved in gene silence. Our results emphasize the exceptional role of MITEs in transcriptional regulation of genes and have general implications to understand interaction between MITEs and their host genome.

Impact of hepatitis C virus genotype 3 on liver disease progression in a Chinese national cohort.

BACKGROUND: Hepatitis C virus (HCV) genotype 3, particularly subtype 3b, is increasing in prevalence and distribution in China. This study evaluated the prevalence, regional distribution, clinical characteristics, host factors, treatment outcomes, and disease progression of patients with HCV genotype 3 in China. METHODS: A 5-year follow-up was preceded by a cross-sectional study. Treatment choices were at the discretion of treating physicians. Estimated infection time to overall-disease-progression (defined by ≥1 of: newly diagnosed cirrhosis; cirrhosis at baseline, Child-Turcotte-Pugh score increased 2 points or more; progression from compensated cirrhosis to decompensated cirrhosis; hepatocellular carcinoma; liver transplantation; or death) was calculated using the Kaplan-Meier method. Cox regression analyses were conducted to evaluate the risk factors for disease progression. RESULTS: The cross-sectional study enrolled 997 patients, including 91 with HCV genotype 3 infection. Among them, subtype 3b (57.1%) was more dominant than subtype 3a (38.5%). Five hundred and twelve patients were included into the follow-up phase. Among patients analyzed for estimated infection time to overall-disease-progression, 52/304 (17.1%) patients with HCV genotype 1 and 4/41 (9.8%) with HCV genotype 3 (4/26 with genotype 3b, 0/13 with genotype 3a, and 0/2 with undefined subtype of genotype 3) experienced overall-disease-progression. Patients with HCV genotype 3 were younger than those with genotype 1 (mean age: 39.5 ±â€Š8.7 vs. 46.9 ±â€Š13.6 years) and demonstrated more rapid disease progression (mean estimated infection time to overall-disease-progression 27.1 vs. 35.6 years). CONCLUSIONS: HCV genotype 3, specifically subtype 3b, is associated with more rapid progression of liver disease. Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions. TRIAL REGISTRATION: NCT01293279, https://clinicaltrials.gov/ct2/show/NCT01293279; NCT01594554, https://clinicaltrials.gov/ct2/show/NCT01594554.

High prevalence of aspirin resistance in elderly patients with cardiovascular disease and metabolic syndrome.

BACKGROUND: Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease (CVD). METHODS: A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome (control group) received daily aspirin therapy (≥ 75 mg) over one month. Platelet aggregation was measured by light transmission aggregometry (LTA). Aspirin resistance was defined as ≥ 20% arachidonic acid (AA)- and ≥ 70% adenosine diphosphate (ADP)-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one (but not both) of these criteria. RESULTS: By LTA, 38 of 469 (8.1%) patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio (OR) = 2.039; 95% confidence interval (CI): 1.047-3.973]. In the multivariate logistic regression analysis, metabolic syndrome (OR = 4.951, 95% CI: 1.440-17.019, P = 0.011) was a significant risk factor for aspirin resistance. CONCLUSIONS: A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients.

Electron microscopic investigation of anterior lens capsule in an individual with true exfoliation.

AIM: To determine the changes which occur in the anterior capsule in true exfoliation which is a very rare condition. METHODS: The anterior capsule from a 93 year-old patient and 6 other patients with age-related cataract during capsulorhexis was examined via transmission electron microscopy (TEM). RESULTS: TEM revealed apoptosis of lens epithelial cells in both two groups. Moreover, we observed lamellar delamination, granular belts in the anterior capsular zone and loss of the subcapsular epithelium cells in the posterior capsular zone, as well as abnormal fibrils located in the central capsular layer only in the sample from the patient with true exfoliation. CONCLUSION: We suggest that loss of lens epithelial cells and appearance of abnormal fibrils is important in disease developing, and our study supported age-related degeneration is one of causative factors in true exfoliation.

Chronic intermittent hypoxia aggravates cardiomyocyte apoptosis in rat ovariectomized model.

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 O2 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 expression of bax and bcl-2 in the OC group was not significantly different from the CIH group, but the ratio of bax/bcl-2 was significantly increased in the OC group (P < 0.05); this was associated with severe cardiomycyte apoptosis in the OC group. TUNEL confirmed this observation. CONCLUSIONS: This study found that CIH may induce oxidative stress in OVX rats but not in CIH rats, and cause more severe cardiomyocyte apoptosis in OVX rats compared with CIH rats. This means that OVX rats exposed to CIH suffered more severe cardiac injury compared with CIH rats due to reduced antioxidation. These findings may partly explain the reason why OSA has a worse cardiovascular impact on menopausal women, and emphasize the importance of detection and early treatment of OSA in menopausal patients.