Establishment of chronic obstructive pulmonary disease rat models by passive cigarette smoking and intratracheal instillation of lipopolysaccharide

AIM:To establish rat chronic obstructive pulmonary disease(COPD) models by passive cigarette smoking plus intratracheal instillation of lipopolysacchride(LPS) or passive cigarette smoking only, which would be similar to the pathogenesis of human COPD. METHODS:48 Wistar rats were randomly divided into 4 groups.(1) Healthy control I group(n=12), rats were bred 4 weeks;healthy control II group(n=12), rats were bred for 3months. (2) Model group I (n=12), 200μg lipopolysaccharide(LPS) was instilled intratracheally once for every two weeks and the rats were exposured to 5% of cigarette smoke, 0.5 h/d for 4 weeks.(3) Model group II(n=12),rats were exposed to 5% of cigarette smoke, 0.5 h/d for 3 months. The pathologic changes of airways and lung tissues, pulmonary function and blood gas analysis were determined. The airway wall lymphocytes and alveolar macrophages were counted. The cross areas of epithelial layer, smooth muscle layer and lamina propria of bronchi were measured. The hydroxyproline of lung tissue homogenates was determined by biochemistry method.RESULTS:The pathologic changes of airways and lung tissue of two models were similar to but milder than those of COPD patients(biopsy data). The collagen deposition and the cross areas of epithelial layer and smooth muscle layer in airway walls of two model groups were significantly increased than those of control groups(P＜0.01,P＜0.05).FEV_0.3/FVC% of two model groups, PaO₂ and SaO₂ of model I group were significantly decreased, while R_i and R_e in model I group were significantly increased than that of control I group(P＜0.05). The PaCO₂ and the counts of lymphocytes and alveolar macrophages of both model groups were significantly increased than those of the control groups (P＜0.01). Lots of alveolar macrophages had phagocyted smoke granules. The amounts of hydroxyproline of two model groups were significantly increased than those of control group((P＜0.05) and were negatively related to the FEV_0.3/FVC%, respectively (P＜0.01,P＜0.01) and positively related to airway resistance of model I group(P＜0.01). CONCLUSIONS:COPD rat models were successfully established by passive cigarette smoking plus intratracheal instillation of LPS and cigarette smoking only. The pathologic changes were similar but milder than those of COPD patients. The airway obstruction of model I group was more severe than that of model II group, but they have no significant difference.     

Plethysmographic comparison of breathing pattern in heaves (recurrent airway obstruction) versus experimental bronchoconstriction or hyperpnea in horses

BACKGROUND: Horses with recurrent airway obstruction (heaves) are described as exhibiting "increased abdominal effort," but it is unknown whether this translates to an effective contribution to ventilation. HYPOTHESIS: We hypothesized that heaves is characterized by asynchrony between rib cage and abdominal motions, and that the abdominal component is the major contributor to ventilation. ANIMALS: The rib cage versus abdominal motion in naturally occurring heaves (n = 15) was compared to controls at rest (n = 7) and during hyperpnea because of lobeline treatment, and the effects of histamine-induced bronchoconstriction in controls (n = 10). METHODS: Flow patterns, phase angle (theta) between the rib and abdominal compartments, abdominal (Vabd) contribution to tidal volume (VT), and lung mechanics were measured. RESULTS: Findings unique to the heaves group included the loss of biphasic expiratory flow, severely increased theta with the abdomen consistently lagging behind the rib cage, and a reduced contribution of the abdomen to ventilation. A subgroup of heaves (n = 5) with abdominal paradox showed a significant (P < .05) reduction in tidal volume, and increased respiratory rate. Bronchodilation reduced theta in heaves (P = .06), but theta remained significantly higher after bronchodilation than found in controls. CONCLUSIONS AND CLINICAL IMPORTANCE: We conclude that breathing pattern in horses with heaves is characterized by severe rib cage/abdominal asynchrony, with the rib cage motion in synchrony with flow, therefore dominating ventilation. In a subset of heaves, the abdominal compartment (diaphragm, abdominal muscles) was completely out of synchrony with flow ("abdominal paradox") despite the clinical appearance of "increased abdominal effort."     

Cigarette dust particles induced lung function injury of chronic obstructive pulmonary disease in mice

AIM: To investigate the pathogenesis of chronic obstructive disease (COPD) in mice by using nasal drip of cigarette dust particles (DSP) induced pulmonary function damage model.METHODS: BALB/c mice were randomly divided into control group, LPS 100 mg/L group, DSP 0.75 mL/L group, DSP 1.5 mL/L group and DSP 3 mL/L group for 30 days. The method of nasal drip was used for 30 days to establish the COPD model. Rrs, Ers, Crs, Est, Cst, P-3/8Rn, P-3/8G and P-3/8H were measured for evaluating lung function of the mice in each group by the method of FlexiVent. The effect on the increase of airway resistance induced by methacholine (Mach) was determined using main bronchial rings by Myograph method. The HE, Masson and Resorcinol fuchsin staining of mouse tracheas and lung tissues were conducted. RESULTS: Continuous nasal drip with DSP for 30 days increased Rrs, Ers, Est, P-3/8Rn and decreased Crs, Cst, P-3/8G and P-3/8H in the mice. DSP significantly shifted the dose-effect curve of tracheal contraction induced by Mach to the left, increased the sensitivity of the airway to Mach, and significantly increased the maximal contractile airway effect of Mach. Exposure to DSP caused fibrosis of airway subepithelial, deposition of collagen in the airway basement membrane under the reticular plate, induced reticular plate thickening, pulmonary bronchial lumen serious deformation, and the inflammatory cell infiltration in the lung of mice. Significantly increased alveolar wall muscle fibers and collagen fibers were also observed. CONCLUSION: The lung function and pathomorphological changes of COPD mice induced by 30 days nasal drip of cigarette dust particles were similar to those of human COPD.     

从“久卧伤气”探讨慢性阻塞性肺疾病合并坠积性肺炎发病机制

长期卧床的慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）患者,痰液等分泌物易阻塞于呼吸道,甚则肺部形成瘀血,极易引发坠积性肺炎。中医认为“久卧伤气”,气伤则虚、气伤痰阻、气伤血瘀,终致痰瘀互结。COPD患者肺、脾、肾虚,痰瘀交阻,久卧于床则加重三脏之虚,痰瘀益甚而合并坠积性肺炎。故从COPD并发坠积性肺炎的中医病机出发,深入剖析“久卧伤气”与COPD并发坠积性肺炎的关系,以期为临床诊疗提供理论基础。     

慢性阻塞性肺疾病的气道反应性与血清IL—8因子水平的研究

目的：探讨慢性阻塞性肺疾病（ＣＯＰＤ）的气道反应性ＩＬ－８因子在ＣＯＰＤ发病中的作用，方法：用组胺气道吸入激发试验观察缓解期ＣＯＰＤ，哮喘和健康人的气道反应性，同时测定气道激发前后血清ＩＬ－８水平变化。结果：ＣＯＰＤ和哮喘患者均呈气道高反应性，且ＣＯＰＤ组ＰＤ５０ＦＥＶ１与ＦＥＶ１／Ｐｒｅ％（Ｐ〈０．０２，Ｐ〈０．０５），ＩＬ－８水平与ＰＤ２０ＦＥＶ１无显著相关性，气道激发后，ＣＯＰＤ和哮喘血清Ｉ     

Endogenous hydrogen sulfide regulates oxidant/antioxidant balance in rat with chronic obstructive pulmonary disease

AIM: To investigate the role of hydrogen sulfide (H₂S) in the protection against oxidative stress in rats with chronic obstructive pulmonary disease (COPD).METHODS: The rat model of COPD was established by cigarette smoking (CS) combined with lipopolysaccharide (LPS) instillation. Thirty-two healthy male Sprague-Dawley rats were randomly divided into 4 groups: control group, CS+LPS group, CS+LPS+NaHS (H₂S donor) group and CS+LPS+PPG (DL-propargylglycine, an inhibitor of cystathionine-γ-lyase) group. After 30 days, the lung functions of the rats were measured, the histological changes of lungs were observed under light microscope and the pathological scores were calculated. The H₂S level in plasma and the protein expression of cystathionine-γ-lyase (CSE) in the lung tissues were measured. The content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and catalase (CAT) were detected to reflect oxidative stress.RESULTS: Compared with control group, the peak expiratory flow (PEF) decreased by 24% and intra-pressure (IP) increased by 66% in CS+LPS group. The pathological scores of the lung tissues also increased. Compared with CS+LPS group, no change in the lung function was observed after given NaHS or PPG, but the pathological scores decreased in CS+ LPS+ NaHS group. Compared with control group, the content of H₂S in plasma was increased by 26% on day 16. Compared with CS+LPS group, the content of H₂S in plasma of CS+LPS+PPG group was decreased by 22% after 30 days. Compared with control group, the protein expression of CSE increased, and no statistical difference among CS+LPS group, CS+ LPS+ NaHS group and CS+LPS+PPG group was observed. Compared with control group, MDA content in the lung tissues was increased by 24% in CS+LPS group, the activity of SOD was increased by 47% and the activity of CAT was increased by 52%. Compared with CS+LPS group, the MDA content in CS+LPS+NaHS group was decreased by 21%, and no statistical difference in the activity of SOD and CAT was observed. The activity of SOD decreased by 33% after given PPG.CONCLUSION: H₂S plays a role as anti-oxidant in the rats with COPD. The CSE/ H₂S pathway may be involved in the development of COPD.     

小城镇社会保障制度建设的意义及相关因素分析

选择了不同城市及农村社会保障的小城镇社会保障问题作为研究对象，重点阐述社会保障制度建设对推动小城镇发展的作用、意义，分析了该制度建设的有利条件，并提出几个尚等解决的制度性难题。     

SONOGRAPHIC EVALUATION OF EXPERIMENTAL BILE DUCT LIGATION IN THE DOG

The common bile duct was surgically ligated in five normal adult dogs. Ultrasonographic examinations of the gallbladder and biliary system were performed after duct ligation at intervals of 24 hours. The sequence of biliary system dilation was from the common duct to the peripheral intrahepatic ducts. Common duct enlargement was evident in 24–48 hours, while peripheral biliary duct dilation was recognized by five to seven days after obstruction. When compared with hepatic and portal veins, dilated biliary ducts were more tortuous and had irregular branching patterns. Gross pathologic changes were correlated with ultrasonographic findings at seven, 14, 15, 18 and 21 days after obstruction.     

Role of Th17/IL-17A in chronic inflammatory airway diseases

The idea has been popular for a long time that Th1/Th2 imbalance is the major cause of many diseases. However, the Th1/Th2 paradigm has encountered increasing challenge since the discovery of a novel subset of Th cells, Th17. Th17 cells secrete a series of cytokines (IL-17A~F, IL-21 and IL-22), which is quite different from those produced by Th1 and Th2 cells. It is now generally accepted that Th17/IL-17A plays a pivotal role in autoimmune and host defense. Although first discovered in autoimmune diseases, emerging studies begin to explore the way in which Th17/IL-17A acts in chronic inflammatory airway diseases, such as asthma and chronic obstructive pulmanary disease. In this review, we will summarize the differentiation and function of Th17, and introduce the progress in the correlation between Th17/IL-17A and chronic inflammatory airway diseases. Further elucidating the mechanism of Th17/IL-17A-related pathophysiological changes will contribute to prevention and treatment of chronic inflammatory airway diseases.     

加味大柴胡汤对阻塞性黄疸老年大鼠TRPC1表达的影响

目的 探讨加味大柴胡汤在临床上辅助治疗老年阻塞性黄疸的理论机制。方法 通过结扎胆总管的外科手术方法建立阻塞性黄疸老年大鼠模型,实验分为假手术组、模型组、加味大柴胡汤组,予以相应干预,分3、7、10 d共3个时间段,每组10只SPF级老年SD大鼠,在各时间段取老年大鼠肝组织及心脏血,检测AST、ALT及TBA;采用钙离子试剂盒检测老年鼠肝组织匀浆钙离子浓度;采用Western Blot法检测老年鼠肝组织TRPC1蛋白的表达,采用Tunel法观察肝细胞凋亡情况。结果 造模成功后各时间点模型组、加味大柴胡汤组与假手术组比较,ALT、AST、TBA和Ca²⁺浓度均升高,且模型组上升更明显（P<0.01）,模型组、加味大柴胡汤组的TRPC1的蛋白含量也均高于假手术组（P<0.01）,且加味大柴胡汤组肝细胞的凋亡率低于模型组（P<0.01）。结论 梗阻性黄疸老年大鼠TRPC1表达明显升高,加味大柴胡汤下调TRPC1的表达,可能是其降低钙超载,减少肝细胞凋亡的机制之一。