Association between preserved ratio impaired spirometry and sleep apnea in a Chinese community.

OBJECTIVE: This study investigated the association between obstructive sleep apnea (OSA) and preserved ratio impaired spirometry (PRISm) in a community population. METHODS: Baseline data from a prospective cohort study, the Predictive Value of Combining Inflammatory Biomarkers and Rapid Decline of FEV1 for COPD (PIFCOPD), were used for cross-sectional analysis. Participants aged 40-75 years were recruited from the community and their demographic information and medical history were collected. The STOP-Bang questionnaire (SBQ) was used to assess the risk of OSA. Pulmonary function tests were performed using a portable spirometer (COPD-6) and forced expiratory volume in 1 s (FEV1) and 6 s (FEV6) were measured. Routine blood, biochemical, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 tests were also performed. The pH of the exhaled breath condensate was determined. RESULTS: A total of 1183 participants were enrolled, of which 221 with PRISm and 962 with normal lung function. The neck circumference, waist-to-hip ratio, hs-CRP concentration, proportion of males, cigarette exposure, number of current smoker, high risk of OSA, and prevalence of nasal and ocular allergy symptoms were significantly higher in the PRISm group than in the non-PRISm group (p < .05). Logistic regression showed that the risk of OSA (odds ratio, 1.883; 95% confidence interval, 1.245-2.848), waist-to-hip ratio, current smoking, and prevalence of nasal allergy symptoms were independently associated with PRISm after correcting for age and sex. CONCLUSION: These findings showed that OSA prevalence is independently associated with PRISm prevalence. Further studies should confirm the relationship between systemic inflammation in OSA, localized inflammation of the airways, and impaired lung function.

Identification of exosome miRNAs in bronchial epithelial cells after PM2.5 chronic exposure.

Numerous epidemiological studies have demonstrated that chronic PM2.5 exposure was associated with the lung carcinogenesis without known potential mechanisms. Exosomes-derived non-coding RNAs, including miRNAs, are proposed to play critical role in the occurrence and development of malignant diseases. So identification of exosomes-derived miRNAs could help us to better understand the molecular toxicity of PM2.5-induced lung cancer. Establishment chronic exposure animal and cell model with PM2.5 was conducted as before. HE staining was used for estimating the histological alternations of lungs in vivo. The expressions of EMT markers in vivo and vitro were quantified by Western blot. Then the exosomes in cell culture supernatant were extracted and the involved miRNAs were extracted and sequenced. The different expression level of miRNAs were verified by RT-PCR. Chronic PM2.5 exposure induced bronchial epithelial cell atypical hyperplasia and massive macrophage infiltration. PM2.5 exposure induce EMT event in vivo and vitro indicated as increased expression of Vimentin and decreased expression of E-cadherin. And five passages of PM2.5 stimulation also induced the release of rich and extractable exosomes in the cell culture supernatant in vitro. Through sequencing, there were differentially expressed 36 miRNAs between PM2.5 chronic exposed and control groups with 1.5-fold and greater differences. Among them, there were 30 exosome-miRNAs upregulated and 6 downregulated expression by PM2.5 exposure. The downregulated expression of miR-29b-2-5p, miR-193b-5p and miR-320c and upregulated expression of miR-100-5p, 125b-5p and unconservative_2_45093 in PM2.5 group were identified and reconfirmed by qRT-PCR. Chronic PM2.5 exposure causes bronchial epithelial cells atypical hyperplasia and induces EMT event in vivo, and it also induce the expression differences of miRNAs in exosome in vitro. Meanwhile, the identified differentially expressed exosome-miRNAs may partially associate with tumorigenesis. To sum up, the identified exosome-miRNAs may play role in the development of lung cancer induced by chronic PM2.5 exposure.

PM2.5-related cell death patterns.

With the increasingly serious problem of environmental pollution, the health problems caused by PM2.5 are gradually coming into our line of sight. Previous researches have indicated that air pollution is nearly related to various diseases, but few studies have focused on the exact function mediated by particulate matter less than 2.5 (PM2.5) in these diseases. PM2.5 is known to induce multiple ways of cell death, including autophagy, necrosis, apoptosis, pyroptosis and ferroptosis. Therefore, it is of much importance to understand the different ways of cell death caused by PM2.5 in the pathogenesis and treatment of PM2.5-related diseases. This present review is an insight of multiple ways of PM2.5­induced cell death in different diseases.

Prevalence of interstitial lung disease in polymyositis and dermatomyositis: A meta-analysis from 2000 to 2020.

OBJECTIVE: Interstitial lung disease (ILD) is the most important prognostic factor for mortality in patients with polymyositis (PM) and dermatomyositis (DM), but the prevalence of ILD in PM/DM may vary between countries. The aim of this study was to determine the overall prevalence of ILD in global patients with PM/DM. METHODS: We performed a systematic literature review of studies published from Jan 1, 2000 to April 30, 2020 on ILD and PM/DM. We extracted data and pooled the prevalence by using a random-effect model due to high heterogeneity. Heterogeneity was assessed by subgroup analysis and sensitivity analysis. RESULTS: A total of 34 studies with 10,130 patients were included in our meta-analysis. Pooled data demonstrated that the global prevalence of ILD in patients with PM/DM was 0.41 (95% confidence interval [CI] 0.35-0.48). However, this prevalence varied with geographical locations and time trends. The prevalence of ILD in PM/DM was 0.5 (95% CI 0.42-0.57) in Asia, 0.23 (95% CI 0.15-0.31) in America, and 0.26 (95% CI 0.18-0.34) in Europe. A higher prevalence of ILD was reported in studies published in 2011-2015 (0.43, 95% CI 0.34-0.52) and 2016-2020 (0.45, 95% CI 0.35-0.54), compared with those published in 2000-2010 (0.27, 95% CI 0.16-0.39). The pooled prevalence of ILD in patients with DM, PM, and clinically amyopathic dermatomyositis subtype was 0.42 (95% CI 0.35-0.49), 0.35 (95% CI 0.27-0.42), and 0.53 (95% CI 0.32-0.74), respectively. Patients with anti-Jo-1 and anti-melanoma differentiation-associated gene 5 antibodies were more likely to develop ILD than other myositis-specific autoantibodies. CONCLUSION: The global prevalence of ILD in patients with PM/DM was approximately 41% and the condition was predominant in Asians. This highlights potential genetic and environmental differences in the pathogenesis of ILD in patients with PM/DM. More studies are required to elucidate the specific associations.

PM2.5 downregulates MicroRNA-139-5p and induces EMT in Bronchiolar Epithelium Cells by targeting Notch1.

PM2.5 was closely linked to lung cancer worldwide. However, the mechanism involved in PM2.5 induced lung cancer is still largely unknown. In this study, we performed chronic PM2.5 stimulation animal and cells model to investigate the carcinogenetic mechanisms of PM2.5 by targeting EMT through Notch1 signal pathway. Next, we focused on the miRNA involved in PM2.5 induced Notch1 pathway activation. We found chronic PM2.5 could induce EMT event in vivo and in vitro, while reducing miR-139-5p expression and activating Notch1 pathway meanwhile. And blocking Notch1 signal pathway by specific small molecule inhibitor could reverse PM2.5 induced EMT. Then, overexpression of miR-139-5p downregulated the expression of Notch1 protein in untreated 16HBE cells. Importantly, overexpression of miR-139-5p blocked Notch1 pathway activation and inhibited EMT event in PM2.5 treated cells. These results indicate that PM2.5 induces EMT event through Notch1 signal pathway and miR-139-5p is a novel regulator of PM2.5-induced EMT by targeting Notch1. Our conclusion is that overexpression of miR-139-5p can down-regulate the expression of Notch1 and reverse the occurrence of malignant lung events induced by chronic exposure to PM2.5.

Predictive Value of Combining Inflammatory Biomarkers and Rapid Decline of FEV1 for COPD in Chinese Population: A Prospective Cohort Study.

Background: In China, the high prevalence and mortality rate of Chronic Obstructive Pulmonary Disease (COPD) and the poor intervention effect makes it into a heavy social burden. The main reason is that the current diagnosis of COPD mainly based on the static lung function, which is difficult for early intervention. Through matching a predictive model for high-risk groups of COPD that rewards FEV1 rapid decline as the core, we will establish the early warning model and prove its validity and socio-economic value. Methods: This is a multi-center, prospective, cohort study. A total of 10,000 people aged 40∼75 without lung disease will be recruited and followed for 3 years. Some questionnaires such as St George's Respiratory Questionnaire (SGRQ), income class, educational level, comorbidity, smoking habit, and biomass smoke exposure history will be collected. The baseline level of Interleukin 6 (IL-6), high-sensitivity C-reactive Protein (hs-CRP), microRNAs-23a (miR-23a) in peripheral blood and pH value in exhaled breath condensate (EBC) will be measured, lung spirometry will be tested in the first, second, and fourth years. Primary outcome is the incidence of COPD, multivariate regression analysis will be used to establish the predictive model for COPD in China. Discussion: With the rapid decline of lung function as the core and the baseline inflammatory biomarkers in peripheral blood and pH of the exhaled breath condensate as affecting factors, a predictive model to achieve early detection of high-risk COPD groups will be established and promoted. Trial registration: This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT03532893) on 21 May 2018, https://register.clinicaltrials.gov.

Identification of long non-coding RNA and circular RNA in mice after intra-tracheal instillation with fine particulate matter.

BACKGROUND: Fine particulate matter (PM2.5) exposure has been proved to be associated with respiratory diseases in epidemiological studies, but the underlying mechanisms are not clear. One of the most important mechanisms involved is inflammation. Non-coding RNAs are proposed to play crucial roles in epigenetic modulation and post-transcriptional regulation. Identification of non-coding RNAs can show us the new insight into the molecular toxicity of PM2.5. MATERIALS AND METHODS: Intra-tracheal instillation of saline or PM2.5 was performed in BALB/c Mice once a week for consecutive eight weeks. Genomewide transcriptome profiling of coding genes, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in mice lung were done by ribosomal RNA-depleted RNA sequencing. Lung histological alternations were observed in haematoxylin and eosin (HE) staining sections. The expressions of pro-inflammatory cytokines and Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome were quantified by qRT-PCR、ELISA and Western blot. RESULTS: 1873 coding genes, 885 lncRNAs and 142 circRNAs were differentially expressed in lung tissues of the saline and PM2.5 exposed mice. The upregulated expressions of lncRNA NONMMUT065867, lncRNA NONMMUT064312, lncRNA NONMMUT018123 and the downregulated expressions of circRNA CBT15_circR_1011, circRNA mm9_circ_005915 were identified by qRT-PCR in PM2.5 group. The pulmonary inflammation score was higher in PM2.5 group. What's more, the expressions of pro-inflammatory cytokines and NLRP3 inflammasome were upregulated in PM2.5 exposed mice. CONCLUSION: PM2.5 causes lung inflammation and increases the expression of NLRP3 inflammasome. The identified novel lncRNAs and circRNAs may paly important role in the development of lung inflammation caused by PM2.5.

PM2.5 induces EMT and promotes CSC properties by activating Notch pathway in vivo and vitro.

Fine particulate matter (PM2.5) has been closely linked to increased morbidity and mortality of lung cancer worldwide. However, the role of PM2.5 in the etiology of lung cancer and the mechanism involved in PM2.5 induced lung cancer are largely unknown. In this study, we performed chronic exposure animal model to investigate the carcinogenetic mechanisms of PM2.5 by targeting the induction of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) properties through Notch1 signal pathway. The antagonism of Notch1 signal pathway was carried out in vitro cell lines of A549 and BEAS-2B to block EMT and CSC. We found that chronic PM2.5 exposure mice lung tissue pathology showed atypical hyperplasia of bronchiolar epithelium. Then, we discovered that chronic PM2.5 exposure induced notable EMT event and obvious CSC properties indicating the developing process of cell malignant behaviors. EMT characterized with decreased protein expression of E-cadherin and increased protein expression of Vimentin. CSC properties induced by chronic PM2.5 exposure characterized with increased cell-surface markers (ABCG2 and ALDH1A1) and self-renewal genes (SOX2 and OCT4). Furthermore, PM2.5 exposure activate Notch signal pathway by increasing expression of Notch1 and Hes1. At last, we blocked Notch signal pathway by inhibitor RO4929097 in vitro to explore the underlying mechanism mediating PM2.5 induced EMT and CSC. We found that blocking Notch1 could prevent PM2.5 induced malignant behaviors including EMT and CSC in A549 and BEAS-2B. These data revealed that the induction of EMT and CSC properties were involved in the lung cancer risk of PM2.5 in vivo, and blocking-up Notch1 may negatively regulate EMT and CSC to suppress the invasion and migration in vitro, thereby putatively serving as a novel therapeutic target for PM2.5 induced lung cancer.

PM2.5 Upregulates MicroRNA-146a-3p and Induces M1 Polarization in RAW264.7 Cells by Targeting Sirtuin1.

Background: Fine particulate matter (PM2.5) exposure is proved to be associated with illnesses, but the mechanism is not clear. Potential effects of PM2.5 on innate immunity have become a hotspot recently. Confronting PM2.5, macrophages are able to be activated and induce inflammatory responses. Whether PM2.5 exposure affects macrophage polarization and associated mechanisms remains to be further explored. Afterwards, whether Sirtuin1 (SIRT1) an important intermediate regulator in various physiological processes takes part in the macrophage polarization induced by PM2.5 is unknown. MiRNAs are acknowledged as key regulator in posttranscriptional modification and our previous study found that miR-146a is a novel biomarker of PM2.5 exposure. Thus, we propose a hypothesis, PM2.5 exposure induces M1 polarization and miR-146a-3p is a potential upstream regulator by targeting SIRT1. Methods: RAW264.7 cells were treated with different concentrations of PM2.5 for 24h. The expressions of cytokines and key molecular markers were detected by qRT-PCR, Western blotting and ELISA. The activation degree of TLRs and NF-κB was assessed by Western blotting. The specific agonist and antagonist of SIRT1 were used to explore the potential role of SIRT1 in M1 polarization induced by PM2.5. MiR-146a-3p mimic and inhibitor were pre-transfected into RAW264.7 cells and the effects on M1 polarization induced by PM2.5 were evaluated. Luciferase analysis was used to identify the binding site of miR-146a-3p and SIRT1. Results: PM2.5 increased the mRNA and protein expression of M1 markers including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in RAW264.7 cells. The protein level of TLR4 was significantly increased and the ratio of phosphorylated NF-κB p65 versus p65 subunit was also elevated in PM2.5 group. PM2.5 decreased the protein level of SIRT1 but not the mRNA expression in vitro and in vivo experiments. Pre-treatment with SIRT1 agonist SRT1720 rescued the PM2.5 induced M1 response. Whereas, SIRT1 antagonist EX527 augment the effect. MiR-146a-3p was upregulated in PM2.5 treated RAW264.7 cells. Luciferase experiments reported that SIRT1 was directly targeted by miR-146a-3p. Overexpression of miR-146a-3p downregulated the expression of SIRT1 protein in untreated RAW264.7 cells. Importantly, inhibition of miR-146a-3p upregulated SIRT1 protein and suppressed M1 polarization in PM2.5 treated RAW264.7 cells. Conclusions: These results suggested that PM2.5 induces the inflammatory M1 polarization and TLR4/NF-κB signal transduction pathway might be involved in the process. MiR-146a-3p is a novel regulator of PM2.5 exerted M1 polarization by targeting SIRT1.

Fine particulate matter (PM2.5) aggravates apoptosis of cigarette-inflamed bronchial epithelium in vivo and vitro.

Fine particulate matter (PM2.5) is an essential risk factor of chronic obstructive pulmonary disease (COPD). Recent studies showed weak association between PM2.5 and COPD incidence, but smokers who exposed to higher PM2.5 concentration had more opportunity to gain COPD. Cigarette smoking is the most important risk factor of COPD. Thus, we hypothesized: the role of PM2.5 played on cigarette-inflamed airways was more significant than normal airways. The study firstly established an animal model of C57BL/6J mice with cigarette smoke exposure and PM2.5 orotracheal administration. After calculating pathological scores, mean linear intercept and mean alveolar area, we found PM2.5 aggravated pathological injury of cigarette-inflamed lungs, but the injury on normal lungs was not significant. Meanwhile, inflammatory factors as T-bet, IFN-γ and IL-1α were tested using qRT-PCR and ELISA. The results showed PM2.5 aggravated inflammation of cigarette-inflamed lungs, but the effect on normal lungs was not significant. The most important pathogenesis of COPD is abnormal apoptosis in airway epithelium, due to oxidative stress following long-term exposure to cigarette smoke. Then, apoptotic responses were detected in lungs. TUNEL analysis demonstrated that PM2.5 promoted DNA fragmentation of cigarette-inflamed lungs, but the effect on normal lungs was not significant. Western-blot and immunohistochemistry showed caspase activated significantly in PM2.5-cigarette smoke exposed lungs and activated caspase 3 located mainly on bronchial epithelium. Next, human bronchial epithelial cells were cultured treated with cigarette smoke solution (CSS) with or without PM2.5. Z-VAD-FMK, a pan-caspase inhibitor, was used to suppress the activation of caspases. After analyzing cell viability, DNA fragmentation, mitochondrial activities and caspase activities, the results clarified that PM2.5 aggravated apoptosis in cigarette-inflamed bronchial epithelial cells and the responses could be suppressed by Z-VAD-FMK. Our results gave a new idea about the mechanism of PM2.5 on COPD and inferred cigarette-inflamed airways were more vulnerable to PM2.5 than normal airways.

A prospective study of salvational intervention with ICS/LABA for reducing chronic obstructive pulmonary disease exacerbation under severe air pollution (SIRCAP) in Beijing: protocol of a multi-center randomized controlled trial.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality all over the world. Acute exacerbation of COPD (AECOPD) not only accelerates the progression of disease, but also causes hospital administration and death events. Epidemiologic studies have shown air pollution is a high risk factor of AECOPD. However, there are rare technics or treatment strategies recommended to reduce severe air pollution related AECOPD. METHODS: This is a multi-center, prospective, randomized and standard treatment parallel control clinical trial. Seven hundred sixty-four stable COPD patients in group B, C and D according to GOLD 2017 will be recruited and equally divided into two parallel groups, salvational intervention (SI group) and control group (CT group). Original treatments for participants include tiotropium (18µg once q.d), budesonide/formoterol (160µg/4.5µg once or twice b.i.d) or budesonide/formoterol (160µg/4.5µg once or twice b.i.d) with tiotropium (18µg once q.d). The savational intervention for SI group is routine treatment plus budesonide/formoterol (160µg/4.5µg once b.i.d) from the first day after severe air pollution (air quality index, AQI ≥200) to the third day after AQI < 200. CT group will maintain the original treatment. The intervention will last for 2 years. Primary outcome is the frequency of AECOPD per year and the secondary outcomes include the incidence of unplanned outpatient visits, emergency visits, hospitalization, medical cost and mortality associated with AECOPD per year. DISCUSSION: The salvational intervention is a novel strategy for COPD management under severe air pollution. Results of the present study will provide reference information to guide clinical practice in reducing the air pollution related exacerbation of COPD. TRIAL REGISTRATION: This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT03083067 ) in 17 March, 2017.

PM2.5 downregulates miR-194-3p and accelerates apoptosis in cigarette-inflamed bronchial epithelium by targeting death-associated protein kinase 1.

Background: Persistent exposure to cigarette smoke or biomass fuels induces oxidative stress and apoptosis in bronchial epithelium, which is one of the most important pathogenic mechanisms of chronic obstructive pulmonary disease (COPD). Fine particulate matter (PM2.5) is an aggravating risk factor of COPD exacerbation. Animal evidence showed PM2.5accelerated lung inflammation and oxidative stress in COPD mice, but the mechanism is still not clear. Recently, we found that miR-194-3p is a novel biomarker of both COPD and PM2.5 exposure, and miR-194 family has been reported to be involved in cell proliferation and apoptosis. Thus, we propose a hypothesis: PM2.5 can accelerate apoptotic response of airway epithelial cells in COPD and miR-194 is a potential involved regulator. Materials and methods: Human bronchial epithelial cells (HBEpiCs) were treated with normal media, cigarette smoke solution (CSS) and PM2.5-CSS for 24 h. miR-194-3p mimics, inhibitors and scrambled controls were non-transfected or pre-transfected into HBEpiCs for 48 h. MircroRNAs and mRNA expression were quantified by qRT-PCR. Protein expression was analyzed by western blotting. Caspase activities, mitochondrial membrane potential and TUNEL-positive cells were detected to analyze apoptosis. Bioinformatics and luciferase analysis were used to identify the predicted binding site of miR-194-3p and potential targets. Results: In our study, we found that PM2.5 significantly aggravated apoptosis in cigarette-inflamed HBEpiCs. miR-194-3p was dramatically downregulated in PM2.5-CSS-treated HBEpiCs. Bioinformatics and luciferase experiments reported that death-associated protein kinase 1 (DAPK1), regulating caspase 3 activities in apoptosis, was directly targeted by miR-194-3p. Inhibition of miR-194-3p increased DAPK1 expression and apoptosis in normal HBEpiCs. Importantly, overexpression of miR-194-3p suppressed apoptosis in PM2.5-CSS HBEpiCs. Conclusion: These results suggested that miR-194-3p was a protective regulator involved in apoptosis pathway and a potential therapeutic target for treatment of bronchial epithelial injury aggravation induced by PM2.5.

A pilot study of blood microRNAs and lung function in young healthy adults with fine particulate matter exposure.

Fine particulate exposure (PM2.5) is a risk factor of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), but the mechanism underlying was not clear. Recent studies found blood microRNAs (miRNAs) are potential indicators of either COPD or PM2.5 exposure, but these results had no unified conclusions. We suggested it was more targeted to find disease related miRNAs first and then observe them during PM2.5 exposure. Firstly, in order to screen COPD associated miRNAs, we identified differentially expressed blood miRNAs contrasting COPD participants (n=6) without diagnose of COPD or related treatment before and matched control (n=6). In total, 21 miRNAs were differentially expressed in COPD individuals and expression of miR-495-3p, miR-223-5p and miR-194-3p were further validated using qRT-PCR. The results showed miR-495-3p and miR-223-5p significantly increased whereas miR-194-3p decreased marginally (P=0.058) in COPD participants. Secondly, in order to recognize the relevance between these miRNAs and PM2.5 exposure, we designed an independent time-series study nested within "low-high-low" pollution levels. The expression of blood miR-495-3p, miR-223-5p and miR-194-3p were detected before and after exposure (n=8). The results showed expression of miR-223-5p increased significantly while expression of miR-194-3p decreased significantly after exposure. The Pearson analysis showed only miR-194-3p showed a positive statistically correlation with lag0-1 forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) during exposure of PM2.5. So miR-194-3p might be a potential regulator in the toxicological pathways of both PM2.5 exposure and COPD. As this was a pilot study, formal and large-scale studies should be planned in the future.

Effects of 5-hydroxytryptamine and 5-hydroxytryptamine 2A/2C agonist on the genioglossus activity and sleep apnea in rats.

BACKGROUND: 5-Hydroxytryptamine (5-HT) is a common neurotransmitter in the brain which plays an important role in the pathogenesis of sleep apnea. Dysfunction of 5-HT and 5-HT(2) receptors may lead to the collapse of the upper airway and the instability of respiratory control, which in turn produce apnea. Genioglossus (GG) is one of the most important oropharyngeal muscles maintaining the upper airway open. The present study aimed to investigate the effects of 5-HT and 5-HT(2) receptor on GG activity and the sleep apnea in Sprague-Dawley (SD) rats. METHODS: Microinjection probes were placed within the fourth ventricle of sixteen SD rats. After recovery for a week, the electromyogram (EMG) of GG was recorded in the anesthetized and vagotomized rats. The changes of GG activity before and after the microinjection of 5-HT or 5-HT(2A/2C) agonist -2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) were observed. Probes were also laid in another eight SD rats. Electroencephalogram (EEG), EMG of neck muscle and respiration were recorded at the same time a week later. The effects of DOI on the occurrence of sleep apnea were explored. RESULTS: Both 5-HT and DOI significantly enhanced the activity of GG just 3 minutes after the completion of injection. The effect of 5-HT disappeared quickly and the effect of DOI lasted for more than 27 minutes. DOI also significantly decreased the post-sigh apnea index in non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep and decreased the spontaneous apnea index only in NREM sleep (P < 0.05, respectively). CONCLUSION: 5-HT and 5-HT(2A/2C) system correlated closely with the pathogenesis of the sleep apnea syndrome and 5-HT receptors may become the target of the drug treatment.

[Effects of 5-HT2 agonist/antagonist on sleep apnea in Sprague-Dawley rats].

OBJECTIVE: To evaluate the effects of 5-HT2 agonist/antagonist Ketanserin on sleep apnea in Sprague-Dawley (SD) rats. METHODS: Twenty adult male SD rats were operated for implantation of EEG and EMG electrodes and a microinjection probe was placed within the fourth ventricle. After recovery for a week, rats were monitored for sleep and respiration in three continuous days. There is no intervention on the first day. Before monitoring, 40 microl ACSF were microinjected into the IV ventricle of the rats on the second day. On the third day before monitoring, 40 microl DOI were microinjected into the IV ventricle of ten rats and 40 microl Ketanserin into another ten ones. RESULTS: Compared with blank control and microinjection of ACSF, DOI significantly reduced the total apnea index (AI) from 18.3 (11.1, 20.3) times/h and 15.2 (11.4, 18.0) times/h to 10.8 (3.1, 14.1) times/h (P=0.005 and 0.005, respectively). Post sign apnea index (PSAI) during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep as well as spontaneous apnea index (SPAI) during NREM sleep were all significantly decreased; (P<0.05, respectively); while it had no effect on SPAI during REM sleep (P>0.05). Neither sleep efficiency (the percent of total sleep time in total monitoring time) nor the time ratio of NREM sleep and REM sleep was significantly changed. In contrast to blank control and microinjection of ACSF, Ketanserin significantly reduced the total apnea index (AI) from 19.2 (13.7, 20.9) times/h and 19.0 (12.9, 21.6) times/h to 13.1 (9.5, 14.9) times/h (P=0.005 and 0.005, respectively). PSAI during NREM and REM sleep were significantly decreased (P<0.05, respectively). SPAI during NREM and REM sleep were changed without statistically significant (P>0.05, respectively). It also had no effects on sleep efficiency and the time ratio of NREM sleep and REM sleep. CONCLUSION: Both 5-HT2 agonist and antagonist decreased the sleep apnea index and had no effects on sleep structure. It shows that the role of 5-HT2 receptor in the respiratory regulation during sleep is complex. The mechanisms involved remain to be studied in future.