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OBJECTIVE To study the mechanism of protection provided by dexmedetomidine against COPD-induced lung injury. METHODS COPD rat model was determined by measuring lung function, and comparing HE staining between two different groups. We got the lung tissue and cells from the control and COPD groups. The cells were divided into three groups: control group, and blank and drug groups that were from the COPD rats. Cell apoptosis, relative gene expression and TNF-α and IL-1β from nutrient solution were measured. RESULTS The TV, PEF, EF50, FEV0.3 and FEV0.3/FVC in COPD group were significantly lower than in control group (1.26±0.17 vs 2.65±0.21; 17.61±0.35 vs 38.55±0.24; 1.20±0.14 vs 1.81±0.06; 2.52±0.28 vs 4.44±0.26; 63.39±0.22 vs 88.45±0.34, p < 0.05, respectively). Cell apoptosis was significantly different in blank and drug groups (21.65±0.86 vs 10.74±0.15; p < 0.05, respectively). The gene expressions of miRNA-146a, p53 and Bcl-2 were significantly downregulated compared with blank group. CONCLUSION Dexmedetomidine protected COPD-induced lung injury by inhibiting miRNA-146a expression to reduce cell apoptosis (Tab. 1, Fig. 3, Ref. 25).

Background: Long-acting anticholinergics are effective bronchodilators in asthma, signifying the functional role of an increased cholinergic tone. However, the underlying mechanisms are largely unknown. We hypothesize that the expression of the neurotrophin brain-derived neurotrophic factor (BDNF) is increased, which promotes remodeling of the airway nervous system and contributes to airway hyperresponsiveness (AHR). Methods: Mice were sensitized to ovalbumin (OA) and challenged acutely or chronically. AHR to methacholine (MCh) was assessed in vivo in control and vagotomized animals and ex vivo in lung slices using MCh and vagal electrical field stimulation (EFS). Expression of the neuronal marker PGP9.5 and BDNF was assessed. Results: Chronic, and not acute OA exposure, increased PGP9.5 expression around the airways by 3.3-fold. OA-induced AHR after acute exposure was not affected by vagotomy, whereas AHR in response to chronic exposure was attenuated. Interestingly, in lung slices, airway narrowing in response to MCh was not altered, whereas the response to EFS was significantly enhanced by OA. The sensitivity or EF50 to EFS increased from 28.0±3.4 to 16.1±2.3 Hz after acute exposure and 13.3±2.2 Hz after chronic OA exposure. The maximal effect was not affected by acute exposure and increased from 10.7±2.0 to 18.4±1.7% airway closure after chronic exposure. This was associated with a 1.6-fold increase in BDNF expression in lung tissue. Conclusion: These results suggest that increased neuronal activity is involved in allergen-induced AHR, in particular in the chronic model, and supports the existence of a remodeling process of the airway nervous system that might be mediated via BDNF.

Long-term exposure to cigarette smoke generates chronic obstructive pulmonary disease (COPD) in guinea pigs, but a comprehensive evaluation of changes in lung function, as assessed by barometric whole body plethysmography (WBP), is lacking.Female guinea pigs were exposed to the smoke of 20 cigarettes/day, 5 days/week, during 10 weeks (COPD group, n = 8), and were compared with unexposed female guinea pigs of the same age (control group, n = 8). WBP was performed in both groups, followed by lung histology.At the end of the exposure period, guinea pigs in the COPD group had higher respiratory frequency, while duty cycle (Ti/Ttot) was unaffected. There was a trend toward minute ventilation (MV) and expiratory flow at the mid-tidal volume (EF50) to be higher in the COPD group. Enhanced pause (Penh) was lower, while time of braking (TB) and time to PEF relative to Te (Rpef) were higher in the COPD group. All guinea pigs exposed to tobacco smoke developed emphysematous lesions in their lungs and gained less body weight than controls.In this COPD model, exposure to cigarette smoke produced changes in WBP characterized by a shallow breathing pattern with decreased Penh and a trend toward increasing EF50 (probably due to decreased elastic recoil), increased TB (suggesting dynamic laryngeal narrowing), and a trend of increasing MV (probably due to a higher metabolic rate). Many of these functional changes resemble those observed in patients with COPD and corroborate the suitability of this guinea pig model for the study of COPD.

ObjectiveTo study the effects of cold-dryness on pulmonary and immunologic function of peripheral T-lymphocytes in chronic obstructive pulmonary disease (COPD) model rats, and to provide references for the prevention and treatment of cold-dryness COPD in the Xinjiang region.MethodsThe COPD model was established with an elastase drip into the trachea combined with smoking. The cold-dryness COPD model was developed by stressing with a cold-dry environment. Success of the model was determined by observation of pathologic lung sections. Rats were sacrificed by exsanguination from the femoral artery and changes of peripheral blood CD4+, CD8+, and CD4+/CD8+ were detected by flow cytometry. Data were analyzed with SAS 11.5 statistical software.ResultsOn the ninetieth day after ending the experiment, Peak expiratory flow in the cold-dryness COPD group was lower than that in the COPD and normal control groups (P

Our previous studies have demonstrated the beneficial effects of Bufei Yishen granules combined with acupoint sticking therapy (the integrated therapy) in chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. Dysfunction of pulmonary surfactant proteins (SPs, including SP-A, SP-B, SP-C, and SP-D) may be included in pathophysiology of COPD. This study aimed to explore the mechanism of the integrated therapy on SPs. COPD rat models were established. The treatment groups received Bufei Yishen granules or acupoint sticking or their combination. Using aminophylline as a positive control drug. The levels of SPs in serum, BALF, and lung were measured. The results showed that the integrated therapy markedly reduced the levels of SPs in serum and increased these indicators in the lung. The integrated therapy was better than aminophylline in reducing the levels of SPs and was better than Bufei Yishen granules in reducing SP-A, SP-C, and SP-D in serum. The integrated therapy was better than aminophylline and Bufei Yishen granules in increasing SP-A, SP-B, and SP-D mRNA in the lung. SP-A and SP-D in BALF were positively correlated with PEF and EF50. The levels of SPs are associated with airway limitation. The beneficial effects of the integrated therapy may be involved in regulating pulmonary surfactant proteins.

Background The integrated therapy of Bufei Yishen granule and acupoint sticking has been used in the treatment of stable chronic obstructive pulmonary disease (COPD) clinically, with remarkable benefits. This study was initiated to observe the effects of the combination of Bufei Yishen granule and acupoint sticking on pulmonary function and morphormetry in a COPD rat model. Methods Rats were randomized into Control, Model, Bufei Yishen (BY), Acupoint sticking (AS), Bufei Yishen + Acupoint sticking (BY + AS) and aminophyline (APL) groups. COPD rats were duplicated by repeated cigarette smoke and bacterial exposures. The rats were treated with normal saline, Bufei Yishen granule, acupoint sticking, Bufei Yishen + Acupoint sticking and aminophylline, respectively, from week 9 through 20. Pulmonary function was measured by using a whole body plethysmograph every 4 weeks. The rats were sacrificed at the end of week 20, and lung tissue histology and ultrastructure was observed under light and electron microscopes. Results The pulmonary function, including tidal volume (VT), peak expiratory flow (PEF) and expiratory flow at 50 % tidal volume (EF50), was markedly decreased from week 8 in COPD rats (P

Feline lower airway disease (FLAD) is a chronic respiratory disease of which there is a lack of information on functional assessment in current veterinary medicine. The purposes of this study were to investigate expiratory pattern and evaluate the diagnostic utility of functional parameters in cats with FLAD. Thirty-three client-owned cats (23 FLAD cats and 10 control cats) were studied. Under quiet tidal breathing, pseudo-tidal breathing flow-volume loop (pTBFVL) was obtained from a barometric whole body plethysmography (BWBP) device. There were significant differences in the shapes of expiratory, but not inspiratory, curves between FLAD and control cats. The incidence of the presence of concave expiratory curve indicating lower airway obstruction was 74% in FLAD cats. To assess the diagnostic utility of pTBFVL indices in cats with FLAD, area under the receiver–operator curve was 0.86 for PEF/EF50 (peak expiratory flow divided by expiratory flow at end expiratory volume plus 50% tidal volume); a cuff-off value of PEF/EF50 >1.51 distinguished normal from FLAD (73.9% sensitivity, 100% specificity). There were no significant differences in traditionally measured BWBP parameters (ie, enhanced pause) between cats with and without FLAD in the present study. In conclusion, underlying change on expiratory flow pattern during natural tidal breathing existed in FLAD cats, and selected pTBFVL indices were useful in discriminating FLAD from normal cats. Tidal breathing pattern depicted by pseudoflow–pseudovolume loops from a BWBP system could be a non-invasive tool for functional assessment in client-owned cats.

A method for the noninvasive measurement of airway responsiveness was validated in allergic BALB/c mice. With head-out body plethysmography and the decrease in tidal midexpiratory flow (EF50) as an indicator of airway obstruction, responses to inhaled methacholine (MCh) and the allergen ovalbumin were measured in conscious mice. Allergen-sensitized and -challenged mice developed airway hyperresponsiveness as measured by EF50 to aerosolized MCh compared with that in control animals. This response was associated with increased allergen-specific IgE and IgG1 production, increased levels of interleukin-4 and interleukin-5 in bronchoalveolar lavage fluid and eosinophilic lung inflammation. Ovalbumin aerosol challenge elicited no acute bronchoconstriction but resulted in a significant decline in EF50 baseline values 24 h after challenge in allergic mice. The decline in EF50 to MCh challenge correlated closely with simultaneous decreases in pulmonary conductance and dynamic compliance. The decrease in EF50 was partly inhibited by pretreatment with the inhaled β2-agonist salbutamol. We conclude that measurement of EF50 to inhaled bronchoconstrictors by head-out body plethysmography is a valid measure of airway hyperresponsiveness in mice.

To determine whether smooth muscle from airways made hyper-responsive by ozone exposure is hyper-responsive in vitro, tracheal smooth muscle strips taken from five dogs with airway hyper-responsiveness induced by ozone exposure were compared with strips from five control animals. On 1 day, airway responsiveness was assessed with dose-response curves of acetylcholine aerosol versus pulmonary resistance. On a second day, five dogs were exposed to ozone (3.0 p.p.m. for 2 h) and five were exposed to filtered air. Then airway responsiveness to acetylcholine was reassessed. All dogs were then killed, the trachea was rapidly removed and strips of smooth muscle were prepared from the central one-third of the trachea. The responsiveness of each strip to electrical field stimulation (contractions inhibitable by atropine and tetrodotoxin) and exogenous acetylcholine was assessed after 2 and 6 h of incubation and washing. Ozone caused a marked increase in responsiveness in vivo to acetylcholine with a fall in mean provocation concentration from 0.15 g % to 0.026 g % (P less than 0.001) while sham exposure had no effect. The responsiveness of muscle strips to electrical field stimulation in ozone-exposed dogs after 2 h of incubation and washing was increased when compared with 6 h of incubation and washing and with the control dogs (P less than 0.05 for EF50, the frequency of stimulation giving 50% maximum contraction). However, responsiveness to exogenous acetylcholine was similar in all strips from both ozone-exposed and control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)