Resveratrol inhibits hypoxia-induced oxidative stress and proliferation in pulmonary artery smooth muscle cells through the HIF-1α/NOX4/ROS signaling pathway / 生理学报

The purpose of the present study was to determine the effects of resveratrol on hypoxia-induced oxidative stress and proliferation in pulmonary artery smooth muscle cells (PASMCs) and the underlying mechanism. Primary rat PASMCs were isolated and cultured in vitro and pretreated with different concentrations of resveratrol (10, 20, and 40 µmol/L) or the NADPH oxidase (NOX) inhibitor VAS2870 (10 µmol/L) for 0.5 h. The cells were then cultured under normoxia (21% O

Problems and thoughts in diagnosis and treatment of chronic obstructive pulmonary disease / 中国实用内科杂志

Chronic obstructive pulmonary disease(COPD) is a preventable and treatable disease with high rate of incidence, disability,and mortality, making COPD a heavy burden worldwide. The Global Initiative for Chronic Obstructive Lung Disease Scientific Committee organized a forum and discussed some controversial topics in COPD, including: diagnosis and assessment; risk factors for disease development, advances in treatment of the stable patient, and the assessment and treatment of exacerbations. This article interprets clinical utility of these contents.

Chronic obstructive pulmonary disease assessment test score correlated with dyspnea score in a large sample of Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The chronic obstructive pulmonary disease assessment test (CAT) is an easy to use health-related quality of life questionnaire, the modified Medical Research Council (mMRC) dyspnea scale is a classic dyspnea scale which is widely used, while the correlation between them is still not clear. This study investigated the use of the Chinese translation of CAT in chronic obstructive pulmonary disease patients and its correlation with the mMRC dyspnea scale.</p><p><b>METHODS</b>The multicenter cross-sectional study was conducted in 329 hospitals throughout China from March 1 to April 30, 2010. Chronic obstructive pulmonary disease patients completed both the assessment test and the dyspnea scale during a single study visit.</p><p><b>RESULTS</b>Six thousand, four hundred and thirty-seven patients were evaluated; 74.9% were male and the mean age was (64.9 ± 10.0) years. Median test scores in dyspnea grades 0 to 4 were 14, 16, 22, 26 and 32, respectively; these differences were statistically significant. The CAT score was moderately correlated with mMRC dyspnea grade (r = 0.579, P < 0.001). There was no significant difference in mean CAT score between males and females, and patients of high and low socioeconomic status. Primary analysis suggested that CAT scores were higher in older patients (>65 years) than in younger patients (≤ 65 years) and increased with duration of formal education, but these findings were repudiated by further analysis of subgroups according to mMRC dyspnea grade.</p><p><b>CONCLUSIONS</b>There was no obvious confounding factor influencing use of the CAT in Chinese patients. CAT scores were moderately correlated with the mMRC dyspnea scale.</p>

Interleukin-18 promoter gene -607C/A polymorphism and tuberculosis risk: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Numerous studies have evaluated the association between interleukin-18 (IL-18) promoter gene -607C/ A (rs1946518) polymorphism and tuberculosis (TB) risk. However, the results remain apparently conflicting. The aim of this study was to investigate whether IL-18-607C/A polymorphism is associated with susceptibility to TB.</p><p><b>METHODS</b>Publications addressing the association between the IL-18-607C/A polymorphism and TB risk were selected from the Pubmed, Cochrane Library, Embase, CNKI and Wanfang databases. Data were extracted from the studies by two independent reviewers. Statistical analysis was performed using RevMan 5.0.25 and STATA 11.0 software.</p><p><b>RESULTS</b>Eight case-control studies with a total of 1166 TB patients and 1734 controls were retrieved. Meta-analysis results showed significant association between IL-18-607C/A polymorphism and TB risk in all comparisons of the A allele versus C allele (OR=1.17, 95% CI 1.05-1.30, P=0.004), AA versus CC (OR=1.43, 95% CI 1.14-1.81, P=0.002), CA+AA versus CC (OR=1.20, 95% CI 1.01-1.42, P=0.04) and AA versus CA+CC (OR=1.30, 95% CI 1.07-1.58, P=0.007). In subgroup analysis by nationality, a significant association between IL-18-607C/A polymorphism and TB risk in the comparisons of A versus C, CA+AA versus CC and AA versus CA+CC (OR=1.22, 95% CI 1.07-1.38, P=0.002; OR=1.31, 95% CI 1.06-1.61, P=0.01; OR=1.32, 95% CI 1.07-1.63, P=0.01, respectively) were found in Chinese population but not in Indian and Iranian populations.</p><p><b>CONCLUSION</b>This study suggests that the -607C/A polymorphism of IL-18 gene would be a risk factor for TB, especially in Chinese population. To further evaluate gene-to-gene and gene-to-environment interactions on -607C/A polymorphism and tuberculosis risk, more studies with thousands of patients are required.</p>

Spectrum and antimicrobial resistance of common pathogenic bacteria isolated from patients with acute exacerbation of chronic obstructive pulmonary disease in mainland of China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bacteria-induced respiratory infection has been long considered to be the major cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, a clear picture about the distribution and drug-resistance of pathogenic bacteria in the lower airways should be helpful for treatment of the disease. So far, data on this topic among Chinese are lacking.</p><p><b>METHODS</b>A surveillance study was performed in consecutive patients with AECOPD at five areas in China between October 2006 and April 2008. The sputum from these patients was cultured and isolated for bacteria. Agar dilution method was used to determine the minimal inhibitory concentrations (MICs) of levofoxacin and other 15 antibiotics against these strains.</p><p><b>RESULTS</b>Three hundred and fifty-nine pathogenic bacterial strains were isolated among 884 patients with AECOPD. The predominant bacteria were Pseudomonas aeruginosa (21.7%), Klebsiella pneumoniae (12.3%), Haemophilus influenzae (14.2%) and Streptococcus pneumoniae (11.7%), followed by Haemophilus parainfluenzae (9.5%), Acinetobacter baumannii (7.8%), Moraxella catarrhalis (6.4%) and Escherichia coli (3.6%). The majority of bacterial pathogens isolated in this study were susceptible to fuoroquinolones, ceftazidime, cefepime and imipenem.</p><p><b>CONCLUSIONS</b>Gram-negative bacilli are the leading pathogens in patients with AECOPD in China. Haemophilus parainfluenzae may be one of the most important pathogens in AECOPD. This study provides evidence for local surveillance of AECOPD pathogens and appropriate choice of antimicrobials in China.</p>

Integripetal rhodiola herb attenuates high altitude-induced pulmonary arterial remodeling and expression of vascular endothelial growth factor in rats / 生理学报

The aim of this study was to investigate the effect of integripetal rhodiola herb on pulmonary arterial remodeling and expression of vascular endothelial growth factor (VEGF) in high altitude pulmonary hypertension in rats. Fifty healthy male Wistar rats were divided into five groups randomly: Plain control group (LC group), 10-day plateau group (H(10) group), 30-day plateau group (H(30) group), 10-day rhodiola-treated plateau group (R(10) group), and 30-day rhodiola-treated plateau group (R(30) group). Each group included 10 rats. The rats in LC group were kept in Chengdu (500 meters above sea level), and rats in H and R groups were kept in Lhasa (3 700 meters above sea level). The rats in R group were daily treated with integripetal rhodiola herb extract (24%, 10 mL/kg) intragastrically for 10 d or 30 d, while rats in LC and H groups were treated with the same volume of saline. Mean pulmonary arterial pressure (mPAP) was detected via a catheter in the pulmonary artery by pressure waveform monitoring. The ratio value of right ventricle weight to left ventricle plus septum weight [RV/(LV + S)] was measured. The microstructure of pulmonary arterioles was examined by electron microscopy. The expression of VEGF in the lung was investigated using immunohistochemistry. The results showed that mPAP and [RV/(LV + S)] in H(10) group and H(30) group were higher than those in LC group (P < 0.05); but there was no significant difference between H(10) group and R(10) group (P < 0.05); and mPAP and [RV/(LV + S)] in H(30) group were lower than those in H(30) group (P < 0.05). Electron microscopy showed that compared to LC group, arteriolar endothelial cells were arranged in a columnar or palisading form, protruding into the lumen, accompanied with luminal stenosis, irregular internal elastic membrane, and proliferation of vascular smooth muscle cells in H groups, which was more obvious in H(30) group than in H(10) group; while these pathological changes were attenuated in the R groups compared to H groups. The levels of VEGF protein in H groups were also higher than those in LC group (P < 0.05); while the expression of VEGF in R(30) group was lower than that in H(30) group. In summary, the results show that the integripetal rhodiola herb can attenuate high altitude-induced pulmonary arterial remodeling in rats, and the inhibition of VEGF protein expression by rhodiola may be one of the mechanisms.

Effects of single nucleotide polymorphisms 869 T/C and 915 G/C in the exon 1 locus of transforming growth factor-beta1 gene on chronic obstructive pulmonary disease susceptibility in Chinese / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The main risk factor for chronic obstructive pulmonary disease (COPD) is cigarette smoking. However, only 10% - 20% of chronic heavy smokers develop systematic COPD. We hypothesized that the inheritance of gene polymorphisms could influence the development of COPD, which was investigated by studying two single nucleotide polymorphisms (SNP) in exon 1 of the transforming growth factor-beta1 (TGF-beta1) gene.</p><p><b>METHODS</b>We enrolled 219 patients with COPD as the research group and 148 healthy people as the control group, all of whom were Chinese Han people. The polymorphisms of the TGF-beta1 gene, 869T/C and 915G/C, were analyzed using the method of amplification refractory mutation system-polymerase chain reaction (ARMS-PCR).</p><p><b>RESULTS</b>The occurrence of the TGF-beta1 gene 869T/C polymorphism in patients with COPD was significantly different from the control group (P < 0.05), in which the relative risk of this disease increased in cases who had the C allele (OR: 1.131, 95%CI: 1.101 - 1.539). There was no increased frequency of TGF-beta1 915G/C gene in COPD patients compared with control subjects (P > 0.05).</p><p><b>CONCLUSIONS</b>The polymorphism 869T/C in TGF-beta1 gene has a significant association with disease occurrence in COPD patients and the C allele might be a risk factor. The homozygous wild-type CC of 869T/C on TGFbeta1 could be a predisposing factor in COPD and those who carry the C allele might have particularly susceptibility to developing COPD.</p>

Simvastatin attenuates bleomycin-induced pulmonary fibrosis in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice.</p><p><b>METHODS</b>Bleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days. We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis.</p><p><b>RESULTS</b>Simvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (I and III) mRNA expression induced by bleomycin. Moreover, simvastatin down-regulated the increased expression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-alpha (TNF-alpha) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore, the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration.</p><p><b>CONCLUSIONS</b>Simvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-beta1 and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.</p>

Simvastatin attenuates lipopolysaccharide-induced airway mucus hypersecretion in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases. This study aimed to examine the effect and mechanisms of simvastatin on airway mucus hypersecretion in rats treated with lipopolysaccharide (LPS).</p><p><b>METHODS</b>Mucus hypersecretion in rat airways was induced by intra-tracheal instillation of LPS. Rats treated with or without LPS were administered intra-peritoneally simvastatin (5 and 20 mg/kg) for 4 days. Expression of Muc5ac, RhoA and mitogen-activated protein kinases (MAPK) p38 in lung were detected by real-time polymerase chain reaction (PCR), immunohistochemistry or Western blotting. Tumor necrosis factor (TNF)-alpha and IL-8 in bronchoalveolar lavage fluid (BALF) were assayed by an enzyme-linked lectin assay and enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Simvastatin attenuated LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5ac hypersecretion at both the gene and protein levels in lung (P <0.05). Moreover, simvastatin inhibited neutrophil accumulation and the increased concentration of TNF-alpha and IL-8 in BALF follows LPS stimulation (P < 0.05). The higher dose of simvastatin was associated with a more significant reduction in Muc5ac mRNA expression, neutrophil accumulation and inflammatory cytokine release. Simultaneously, the increased expression of RhoA and p38 MAPK were observed in LPS-treated lung (P <0.05). Simvastatin inhibited the expression of RhoA and p38 phosphorylation in lung following LPS stimulation (P < 0.05). However, the increased expression of p38 protein in LPS-treated lung was not affected by simvastatin administration.</p><p><b>CONCLUSIONS</b>Simvastatin attenuates airway mucus hypersecretion and pulmonary inflammatory damage induced by LPS. The inhibitory effect of simvastatin on airway mucus hypersecretion may be through, at least in part, the suppression of neutrophil accumulation and inflammatory cytokine release via inactivation of RhoA and p38 signaling pathway.</p>

Increased expression of human calcium-activated chloride channel 1 is correlated with mucus overproduction in the airways of Chinese patients with chronic obstructive pulmonary disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic obstructive pulmonary disease (COPD) is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 (CaCC(1)) was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of CaCC(1) and mucus overproduction in the airway of Chinese patients with COPD, the expressions of CaCC(1), MUC5AC and mucus in bronchial tissues were examined.</p><p><b>METHODS</b>Bronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to July in 2004. Twenty-five patients were diagnosed as the patients with COPD overproduction, and other 20 were the control subjects. The expressions of CaCC(1), MUC5AC and mucin in bronchial tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization with digoxigenin (DIG)-labeled RNA probe, immunohistochemical and alcian blue-periodic acid Schiff (AB-PAS) staining, respectively.</p><p><b>RESULTS</b>Compared with the control group, the stronger expressions of CaCC(1) were further detected throughout the bronchial tissues from patients with COPD (P < 0.01). Furthermore, the stronger expressions of the CaCC(1) mRNA were related to the severity of airflow obstruction. Samples from COPD showed a stronger staining for MUC5AC than those in control subjects (P < 0.01) and AB-PAS staining revealed more mucins in COPD patients' submucosal gland comparing with that in control subjects (P < 0.01). Expression levels of the CaCC(1) mRNA were respectively negatively correlated with the patients' forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) data, FEV(1)% predicted data, V(50)% predicted data, V(25)% predicted data (r = -0.43, r = -0.43, r = -0.35, r = -0.36, P < 0.01, P < 0.01, P < 0.05, P < 0.05). While the expression levels of the CaCC(1) mRNA were well correlated with the expression levels of the MUC5AC mRNA of airway epithelium and the PAS-AB stained area of submucosal glands (r = 0.39, r = 0.46, P < 0.05, P < 0.01). Expression levels of the MUC5AC mRNA were negatively correlated with the patients' FEV(1)/FVC data (P = 0.01), FEV(1)% pred data (P = 0.01), V(50)% predicted data, V(25)% predicted data (r = -0.53, r = -0.53, r = -0.48, r = -0.43, P < 0.01, P < 0.01, P < 0.01, P < 0.01). While the expression levels of the MUC5AC mRNA were well correlated with the positively PAS-AB stained area of submucosal gland (P < 0.05), and the correlation coefficients were 0.43.</p><p><b>CONCLUSION</b>These results suggest that the stronger gene expression of CaCC(1) exists, complicated with mucus overproduction in the airway of Chinese patients with COPD.</p>