Effect of endothelin-1 on inflammation and oxidative stress in COPD

AIM:To investigate the effect of endothelin-1 on inflammation and oxidative stress in chronic obstructive pulmonary disease (COPD). METHODS:Healthy non-smokers (30 cases), healthy smokers (30 cases) and COPD patients (29 cases) were collected and induced to produce sputum. The concentration of endothelin-1 in the induced sputum was detected. The model of emphysema was established by cigarette smoke extract to stimulate SD rats. Endothelin A receptor antagonist BQ123 and non-selective endothelin receptor antagonist bosentan were used to intervene with the model rats. The experiment was divided into control group, cigarette-treated group, selective antagonist group and non-selective antagonist group. The protein levels of cleaved caspase-3 in the lung tissue were determined by Western blot. Gelatin zymography was used to analyze the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the lung tissue. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The bioantioxidant power (BAP) was detected by BAP assay kit. RESULTS:The concentrations of endothelin-1 in induced sputum of healthy smokers and COPD patients were significantly higher than that of healthy non-smokers (P<0.05), and the level of endothelin-1 in COPD patients was significantly higher than that in healthy smokers (P<0.05). The levels of cleaved caspase-3, MMP-2, MMP-9, TNF-α and IL-1β in the lung tissues from cigarette-treated group were significantly higher than those in control group (P<0.05). The endothelin A receptor antagonist significantly inhibited the levels of cleaved caspase-3, MMP-2, MMP-9, TNF-α and IL-1β (P<0.05). The serum BAP in cigarette-treated group was significantly lower than that in control group (P<0.05). However, endothelin A receptor antagonist significantly increased serum BAP (P<0.05). CONCLUSION:Endothelin-1 may play an important role in the development and progression of COPD through regulating apoptosis, matrix metalloproteinase activity, inflammation and oxidative stress.     

Effects of N-acetylcysteine on Clara cells and CC16 in rat COPD model

AIM: To investigate the effects of N-acetylcysteine (NAC) on the number of Clara cells and secretion of Clara cells secretory protein (CC16) in rat chrohic obstructive pulmonary disesae (COPD) model.METHODS: Thirty rats were divided into control, COPD and NAC groups (n=10). The change of Clara cell ultrastructure was detected through transmission electron microscope. The number of Clara cells and synthesis of CC16 were measured by immunohistochemistry. The CC16 levels in bronchoalveolar lavage fluid (BALF) and serum were tested by ELISA. The level of CC16 mRNA in lung was determined by RT-PCR.RESULTS: The percentage of Clara cells in terminal bronchioles in the COPD group was significantly decreased than that in the control (P<0.01), and the percentage in NAC group was significantly higher than that in COPD group (P<0.01). The levels of CC16 in the BALF and serum in COPD group were significantly lower than those in control group (P<0.01, respectively), and the levels of CC16 in NAC group were significantly higher than those in COPD group (P<0.05, respectively). The expression of CC16 mRNA in COPD group was weaker than that in control group and NAC group (P<0.01, respectively).CONCLUSION: The number of Clara cells and the secretion of CC16 decrease in a rat model of COPD. Antioxidant NAC can enhance the synthesis and secretion of CC16, which may be a mechanism for the suppression of airway inflammation.     

Progress on role of CCN1 in pulmonary diseases

Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) is an extracellular matrix-associated signaling protein consisting of 381 amino-acid residues, which has the regulatory function for a multitude of cellular responses. The pleiotropic effects of CCN1 on the initiation and resolution of inflammation as well as oncogenesis and development of tumor were reported. According to the numerous data from experimental and clinical studies, this article provides an overview on CCN1 and summarizes the latest understanding of the role of CCN1 in pulmonary diseases.     

长期氧疗对慢性阻塞性肺病患者的疗效分析

目的：探讨长期氧疗(LTOT)对慢性阻塞性肺病(COPD)患者的疗效。方法：对46例COPD稳定期患者进行3a的LTOT、于LTOT前及LTOT后观察患者住院次数、呼吸困难改善情况、动脉血气分析及血浆白蛋白的变化情况。结果：氧疗后1、2、3a与氧疗前基础值比较,患者住院次数减少,呼吸困难等临床症状显著减轻,低氧血症改善,营养状况好转。结论：合理使用LTOT对COPD患者有良好的治疗作用．可提高患者生活质量。     

Plasma and Pulmonary Fluid Endothelin in Horses with Seasonal Recurrent Airway Obstruction

Background: Summer pasture-associated recurrent airway obstruction (SPA-RAO), a seasonal airway obstructive disease of horses, is characterized by clinical exacerbation after exposure to pasture during warm months of the year. Endothelin (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory mediator, has been implicated in the pathogenesis of asthma and equine heaves.
Hypothesis: Immunoreactive ET-1 concentrations increase during clinical exacerbation and return to basal values during periods of disease remission.
Animals: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected.
Methods: Prospective, observational study. Bronchoalveolar lavage fluid (BALF), arterial and venous plasma samples, and clinical variables were obtained from affected horses during clinical exacerbation and remission. Samples and data of nonaffected horses were collected during the summer and winter on dates similar to affected horses. Immunoreactive ET-1 was determined using a commercial ELISA.
Results: The median and range ET-1 concentrations (pg/ml) in arterial (1.3, 0.7–1.8) and venous (1.3, 1.2–1.7) plasma and in BALF (0.3, 0.2–0.4), and pulmonary epithelial lining fluid (PELF) (25.5, 21–50) were greater in affected horses during clinical exacerbation compared with remission ( P < .01). The concentrations of immunoreactive ET-1 were greater in affected horses during clinical exacerbation compared with nonaffected horses ( P < .05).
Conclusions and Clinical Importance: During clinical exacerbation of SPA-RAO, ET-1 is increased in circulation and pulmonary secretions. Intervention with ET receptor antagonists should provide further information on the role of ET-1 in SPA-RAO.     

输尿管镜治疗输尿管结石合并梗阻性脓肾36例

目的总结输尿管镜治疗输尿管结石合并梗阻性脓肾的经验。方法输尿管镜检查中发现输尿管结石合并梗阻性脓肾36例,直视下通过结石留置F5双J管引流,配合有效的抗生素治疗;二期行输尿管镜下弹道碎石或钬激光碎石。结果 26例感染控制后行输尿管镜下碎石成功;10例引流后发现结石已排出或逆行入肾,行体外冲击波碎石。所有患者未出现脓毒血症。结论分期输尿管镜治疗输尿管结石合并梗阻性脓肾可获得良好疗效。     

Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two Warmblood families

Reasons for performing study: The horse owner assessed respiratory signs index (HOARSI‐1–4, healthy, mildly, moderately and severely affected, respectively) is based on owner‐reported clinical history and has been used for the investigation of recurrent airway obstruction (RAO) genetics utilising large sample sizes. Reliable phenotype identification is of paramount importance in genetic studies. Owner reports of respiratory signs have shown good repeatability, but the agreement of HOARSI with an in‐depth examination of the lower respiratory tract has not been investigated. Objectives: To determine the correlation of HOARSI grades 3/4 with the characteristics of RAO and of HOARSI‐2 with the characteristics of inflammatory airway disease. Further, to test whether there are phenotypic differences in the manifestation of lung disease between families. Methods: Seventy‐one direct offspring of 2 RAO‐affected Warmblood stallions (33 from the first family, 38 from the second) were graded as HOARSI‐1–4 and underwent a clinical examination of the respiratory system, arterial blood gas analysis, endoscopic mucus scoring, cytology of tracheobronchial secretion (TBS) and bronchoalveolar lavage fluid (BALF), and clinical assessment of airway reactivity to methacholine chloride. Results: HOARSI‐3/4 animals in clinical exacerbation showed signs consistent with RAO: coughing, nasal discharge, abnormal lung sounds and breathing pattern as well as increased numbers of neutrophils in TBS and BALF, excessive mucus accumulation and airway hyper‐responsiveness to methacholine. HOARSI‐3/4 horses in remission only had increased amounts of tracheal mucus and TBS neutrophil percentages. Clinical phenotypes were not significantly different between the 2 families. Conclusions and clinical relevance: HOARSI reliably identifies RAO‐affected horses in our population.     

Effects of N-acetylcysteine combined with azithromycin on oxidative stress in rats with chronic obstructive pulmonary disease

AIM: To investigate the effects of N-acetylcysteine (NAC) combined with azithromycin (AZI) on oxidative stress in the rats with chronic obstructive pulmonary disease (COPD). METHODS: Male Wistar rats (n=60) were randomly divided into control group, model group, AZI intervention group,NAC intervention group and AZI+NAC group. The COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide. Each day 30 min prior to smoking, intragastric administration with AZI, NAC or combination of the 2 drugs was given for AZI, NAC, and AZI+NAC groups, respectively. On the 31st day, all rats were killed following lung function test. Cell counts of bronchoalveolar lavage fluid (BALF) were performed, and the contents of interleukin-8 (IL-8), interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) in BALF were measured by ELISA. The histopathology of the lung tissues was observed under light microscope, and the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the lung homogenate were measured. RESULTS: Compared with control group, the other 4 groups showed decreased pulmonary function, and inflammatory cell infiltration and alveolar destruction in histopathology. Compared with control group, the other groups showed higher white blood cells, monocyte-macrophages, neutrophils and lymphocytes in the BALF (P<0.05). Compared with model group, AZI group and NAC group, lower white blood cells, neutrophils and lymphocytes in the BALF were observed in AZI+NAC group (P<0.05). Compared with model group, IL-8, IL-17, TNF-α and MDA in AZI group, NAC group and AZI+NAC group significantly decreased (P<0.05), while SOD and GSH-Px significantly increased (P<0.05). Compared with AZI or NAC group, IL-8, IL-17, TNF-α and MDA in AZI+NAC group significantly decreased (P<0.05), while SOD and GSH-Px increased significantly (P<0.05). CONCLUSION: Both NAC and AZI attenuate the lung inflammation and oxidative damage in COPD model rats. Combined medication exerts preferable anti-oxidation effects, which might be more suitable for the treatment of COPD.     

miR-181a regulates CSE-induced autophagy dysfunction and releases of pro-inflammatory factors in NR8383 alveolar macrophages

AIM:To investigate the effect of microRNA-181a (miR-181a) on cigarette smoke extract (CSE)-induced autophagy disorder and releases of pro-inflammatory factors in NR8383 rat alveolar macrophages. METHODS:The NR8383 cells were treatment with 5%,10% and 20% CSE. The release levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-8 were measured by ELISA. The level of miR-181a was detected by RT-qPCR. The numbers of autophagosomes were observed by Cyto-ID staining. The expression levels of LC3-Ⅱ, beclin-1 and p62 were determined by Western blot. NR8383 cells were pretreated with autophagy inhibitor 3-methyladenine (3-MA) or autophagy agonist rapamycin (Rapa) before treatment with 20% CSE, and the release levels of TNF-α, IL-6 and IL-8 were measured by ELISA. Furthermore, NR8383 cells were transfected with miR-181a mimic or miR-181a inhibitor before treatment with 20% CSE, and the release levels of TNF-α, IL-6 and IL-8, and the expression of LC3-Ⅱ, beclin-1 and p62 were detected by ELISA and Western blot, respectively. RESULTS:CSE increased release levels of pro-inflammatory factors and autophagy disorder in a concentration-dependent manner in the NR8383 cells (P<0.05). 3-MA increased CSE-induced releases of pro-inflammatory factors. However, Rapa partially reversed CSE-induced releases of pro-inflammatory factors. Additionally, miR-181a mimic inhibited CSE-induced releases of pro-inflammatory factors and promoted autophagy. However, miR-181a inhibitor increased CSE-induced releases of pro-inflammatory factors and autophagy disorder. CONCLUSION:miR-181a regulates CSE-induced releases of pro-inflammatory factor in the NR8383 cells, which may be related to the regulatory role of miR-181a in autophagy disorder.     

导致母猪繁殖障碍性疾病的原因及防制措施

近几年,吉林省双辽市大力发展牧业经济,养猪业规模不断扩大,母猪的存栏量大幅度提高。但有些规模化养猪场母猪因在产仔季节感染繁殖障碍疾病,给养殖场造成巨大经济损失。笔者结合多年实践,就导致母猪繁殖障碍性疾病的原因及防制措施作一简要介绍,供养殖场（户）参考。