慢性阻塞性肺疾病模型大鼠肺组织差异基因的表达：正常组、模型对照组及中药治疗组的比较

背景：许多疾病都伴有基因表达的改变，能够为认识疾病的发病机制及治疗提供有价值的线索。 目的：采用基因芯片技术筛查慢性阻塞性肺疾病模型大鼠肺组织中差异基因的表达情况。 设计：开放性实验。 单位：山东中医药大学附属医院，解放军军事医学科学院放射与辐射医学研究所，山东中医药大学。 材料：实验于2005-04／10在山东中医药大学附属医院中心实验室进行。①选取SPF级健康雄性50d龄Wistar大鼠15只，随机数字表法分为正常组、模型对照组、中药治疗组，5只／组。②基因芯片类型为大鼠BiostarR-40S（上海博星基因芯片有限公司，批号G050510010052）。 方法：①模型对照组、中药治疗组大鼠采用改良烟熏＋气管滴加脂多糖的方法建立慢性阻塞性肺疾病模型。光学显微镜下观察大鼠气道病理改变，若出现气道黏膜充血水肿，上皮细胞变性坏死，肺内支气管的管腔及周围慢性炎性细胞浸润，管壁周围平滑肌和纤维细胞增生；间隔变薄、断裂，肺泡扩大融合；小动脉血管壁增厚，管腔变小，周围炎性细胞浸润，说明造模成功。②造模成功后第30天，中药治疗组灌服浓度为0．65g／mL的自制中药合剂（麻黄，杏仁，黄芪等），2mL/次，1次／d，连续给药14d。模型对照组每天给予2mL生理盐水灌胃。正常组不做任何干预，相同室内环境下自由饮食饮水。③给药完毕后处死各组大鼠，进行总RNA提取、探针的标记与杂交、洗片，采用芯片图像分析软件分析芯片灰度扫描图，得到芯片上每个基因点的原始信号值（包括前景信号值和背景信号值），从而进行差异表达基因的判定。检验水准是Ratio值大于2．0为上调基因，小于0．5为下调基因。为了提高检验的可靠性，本实验将检验水准设为Ratio值〉2．5为上调基因。Ratio值〈0．375为下调基因。 主要观察指标：①与正常组比较模型对照组的差异表达基因。②与正常组比较中药治疗组的差异表达基因。③与模型对照组比较中药治疗组的差异表达基因。 结果：15只大鼠全部进入结果分析。①模型对照组的基因表达情况较正常组有明显变化，差异表达基因达57个，涉及免疫、代谢、信号转导、基因表达调控、细胞周期、细胞转运、细胞迁移及纤维化等。②中药治疗组的基因表达大多恢复到正常组水平，与正常组比较差异表达基因减少到11个，涉及应激反应、信号转导及细胞骨架等。③与模型对照组比较，中药治疗组的差异表达基因有7个，涉及免疫及神经递质的分泌。 结论：大量的基因表达改变可能是慢性阻塞性肺疾病发病机制的原因之一，而经药物治疗后，大多数差异表达基因能够恢复到正常水平，有利于纠正慢性阻塞性肺疾病的病理改变。     

黏蛋白在慢性阻塞性肺疾病大鼠肺组织中的研究

慢性阻塞性肺疾病的病理特点是呼吸道黏液高分泌,黏蛋白是气道黏液的主要成分,二者关系密切,本文就二者关系做一综述.     

慢性阻塞性肺疾病的康复治疗

慢性阻塞性肺疾病(COPD)是人类死亡及致残的主要原因之一,其康复治疗已日益受到重视.早在1974年美国胸科医师学会肺康复委员会曾对肺疾病康复下一定义:“肺疾病康复可视为临床医学中的专门学科.通过精确诊断、治疗、心理支持和宣教等,制订出针对个人的康复程序以逆转或稳定肺疾病的病理生理或精神病理学的变化,使患者恢复到病损后的最佳功能状态,并经受各种生活场合的考验.此定义要求康复医师在制订康复程序时,要遵从①个体化原则;②综合康复治疗原则;③重视病理生理及精神病理学变化的原则.一个成功的肺康复程序一定要适应每个患者的具体情况,由有经验的医师协调运用多种康复措施,同时调动心理和社会的有利因素,以强化各种治疗效果.     

慢性阻塞性肺疾病治疗进展

慢性阻塞性肺疾病（COPD）患病率和死亡率较高，是一种不可逆转且进行性加重的呼吸疾病。本文重点从避免暴露于危险因子、稳定期和急性加重期的处理等方面进行阐述。     

慢性阻塞性肺疾病的治疗进展

慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）是一种可以预防、可以治疗的疾病,以不完全可逆的气流受限为特点,气流受限常呈进行性加重,且多与肺部对有害颗粒或气体,主要是吸烟的异常炎症反应有关.虽然COPD累及肺,但也可以引起显著的全身效应^[1,2]. 目前,COPD在我国居疾病经济负担的首位.预计2020年COPD将位居世界死亡原因的第三位和世界经济负担的第五位.[第一段]     

血小板与慢性阻塞性肺疾病

慢性阻塞性肺疾病(慢阻肺,COPD)是多种病因引起的慢性气道阻塞,其主要病理生理改变为:阻塞性通气功能障碍,后期发展为肺动脉高压、肺心病.慢阻肺肺动脉血栓形成率达20～50%,合并严重肺动脉高压者血栓形成率更高.血小板具有粘附、促凝和收缩血块的功能,因此在血栓形成和血管损伤中起重要作用.     

慢性阻塞性肺疾病的治疗进展

慢性阻塞性肺疾病对患者的身体健康和生活质量有严重的危害。对该疾病的治疗、研究,具有很重要的意义。本文主要对慢性阻塞性肺疾病治疗进展进行总结。希望能够为相关方面的研究提供参考。     

慢性阻塞性肺疾病肺康复治疗新进展

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是全球患病率及死亡率较高的重要疾病。肺康复治疗通过肺康复计划改善患者的呼吸困难,提高运动耐力及生活质量,改善患者心理障碍及社会适应能力。本文就有关肺康复治疗进展综述如下。     

黄芪对慢性阻塞性肺疾病模型大鼠气道重塑的影响

目的：探讨黄芪对慢性阻塞性肺疾病（COPD）模型大鼠气道重塑的影响。方法：采用熏吸香烟加气管内注射脂多糖的方法建立大鼠COPD模型，测定黏膜下炎症细胞、肺小动脉、支气管壁的变化。结果：治疗组支气管黏膜下炎症细胞数较模型组明显减少（P〈0.01）；治疗组肺小动脉管壁厚度明显较模型组薄，差异有显著性（P〈0.05）；治疗组细支气管平滑肌厚度亦明显较模型组薄，差异有显著性（P〈0.05）。结论：黄芪能够减缓COPD患者的气道重构，延缓或阻止COPD疾病的发展。     

降纤酶治疗慢性阻塞性肺疾病的疗效观察

目的：观察加用降纤酶治疗对提高中晚期慢性阻塞性肺疾病（ＣＯＰＤ）疗效的影响，方法：将５８例中晚期ＣＯＰＤ患者随机分为２组，对照组２８例采用抗炎，化痰，吸氧，扩张支气管及强心等常规治疗，治疗组３０例在常规治疗基础上加用降纤酶５Ｕ加入２００ｍｌ生理盐水中静滴，每日１次，疗程为３日，观察２组症状，体征及动脉血气，纤维蛋白原等指标的改善情况，结果：治疗３日后治疗组的症状缓解率（１００．０％），干，湿性罗音     

细菌诱导大鼠慢性阻塞性肺疾病中结缔组织生长因子的mRNA表达

目的:研究结缔组织生长因子的mRNA在细菌感染导致的慢性阻塞性肺疾病大鼠肺组织中的表达。方法:以适量肺炎链球菌反复经气管穿刺注射感染大鼠,制作大鼠慢性阻塞性肺疾病模型,在感染后的不同时间段处死大鼠,采用实时荧光定量PCR,对大鼠肺组织中结缔组织生长因子的mRNA表达情况进行研究。结果:生理盐水对照组结缔组织生长因子mRNA的表达明显低于肺炎链球菌组(P<0.01)。同时,肺炎链球菌组结缔组织生长因子mRNA的表达随着细菌感染时间的增加而升高(P<0.01)。结论:大鼠长期反复细菌感染可诱导慢性阻塞性肺疾病,其机制可能和结缔组织生长因子表达上调有关。     

Epidemiology of chronic obstructive pulmonary disease in Japan--international comparison

Substantial variation among countries has been reported regarding mortality data for COPD in industrialized countries. Differences in COPD death rates among countries have attracted considerable attention, with multiple suggested hypothesis, including smoking behaviors, air pollution, respiratory infections and genetic factors. However, the lack of standardization of death certification as well as differences among countries in diagnostic standards of COPD, could limit the interpretation of the data. No meaningful international comparisons of COPD prevalence can be possible until a GOLD initiative bring information about COPD to public health officials, the medical community, and the public throughout the world. No comparable data regarding the COPD epidemiology such as Nippon COPD Epidemiology(NICE) study, has been available in other countries than Japan. NICE study indicated that most of COPD cases(90%) are undiagnosed, and a significant attention will be required to raise awareness of COPD.     

Testing the functional status model in patients with chronic obstructive pulmonary disease

BACKGROUND: Patients with chronic obstructive pulmonary disease usually experience gradual functional status degradation, especially dyspnoea, which may affect their daily activities and, eventually, quality of life. A full understanding of both their physiological and psychological functional status is therefore beneficial for effective treatment and helping patients regain or maintain control of their lives. METHOD: Based on a non-experimental research design, 138 patients to test a hypothesized model of functional status in patients with chronic obstructive pulmonary disease, using structural equation modelling, were recruited from a medical center. Data were collected using questionnaires, 6-minute walking distance measurement, and pulmonary function test results recorded in patients' medical records. The proposed functional status model incorporated the exogenous variables disease severity and dyspnoea, and the endogenous variables age, exercise tolerance, fatigue, depression, anxiety, health perception and functional performance. Structural equation modelling with the lisrel software was used to establish a functional status model with those exogenous and endogenous variables. RESULTS: The results indicated a good fit between the proposed functional status model and the data collected [chi(2) = 8.84, P = 0.64, chi(2)/d.f. = 0.80, Goodness of Fit Index (GFI) = 0.98, adjusted GFI (AGFI) = 0.95, root mean square residual (RMR) = 0.04, Critical N (CN) = 384.26]. Coefficients for paths in the functional status model all demonstrated statistical significance. CONCLUSION: The functional status model was shown to consist of functional performance, functional capacity and other concepts, including disease severity, dyspnoea, age, exercise tolerance, fatigue, depression, anxiety and health perception. These results can be used to develop a suitable functional status model for chronic obstructive pulmonary disease, and could act as a reference for formulating future strategies and intervention procedures for further development of functional status.     

A comparison of twice- versus once-weekly supervision during pulmonary rehabilitation in chronic obstructive pulmonary disease

OBJECTIVE: To compare the effects of twice- versus once-weekly supervised pulmonary rehabilitation on exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective, randomized, parallel-group study. SETTING: Hospital outpatient physiotherapy department. PARTICIPANTS: Patients with COPD. INTERVENTION: Group 1 (n=46) received 1 supervised exercise session a week and 2 unsupervised sessions; group 2 (n= 45) received 2 supervised exercise sessions a week and 1 unsupervised session for 6 weeks. Patients were assessed at baseline and at 6 weeks, 2 months, and 6 months. MAIN OUTCOME MEASURES: Incremental (ISWT) and endurance (ESWT) shuttle walk tests and Chronic Respiratory Disease Questionnaire (CRDQ). RESULTS: Sixty-six of 91 patients (group 1, n=34; group 2, n=32) completed the 6-week program. There was no significant difference in key outcome measures between the 2 groups (ISWT, 13.50m; 95% confidence interval [CI], -10.06 to 37.15m; ESWT, 72.64s; 95% CI, -96.01 to 241.29s; CRDQ total score, 2.54; 95% CI, -3.16 to 8.24). The results of the ESWTs suggest there may be an interaction between baseline exercise capacity and benefit of pulmonary rehabilitation, with more disabled patients achieving greater benefit if they are supervised twice weekly. Irrespective of group, allocation benefits after pulmonary rehabilitation had almost dissipated by 6 months. CONCLUSIONS: There was no difference in the effectiveness of twice- versus once-weekly supervised pulmonary rehabilitation. This study highlights the need for development of strategies that will maintain the improvement achieved by the initial pulmonary rehabilitation program.     

Coping and adjustment in Chinese patients with chronic obstructive pulmonary disease

The purpose of this study was to examine the relationships between coping and psychosocial adjustment of Chinese patients with chronic obstructive pulmonary disease (COPD). A convenience sample of 54 hospitalized COPD adult patients participated in the study. All participants had moderate to severe scores in respect of pulmonary functional status and symptoms. The findings indicated that the participants adopted limited coping strategies and had poor psychosocial adjustment to their illness. No significant correlation was found between the total scores for coping and psychosocial adjustment. Both confrontive and optimistic coping scores of the perceived use and helpfulness of the coping scale were negatively correlated with the total adjustment score. Fatigue, older age, worse perception of current health status, and use of confrontive and emotive coping styles were predictors of worse psychosocial adjustment. This study provides a better understanding of the needs and difficulties experienced by Chinese COPD patients and concludes that modification of such factors by health professionals may lead to a better psychosocial adjustment.     

骨桥蛋白在慢性阻塞性肺疾病小鼠肺组织中的表达以及细辛脑的干预作用

目的初步研究骨桥蛋白(OPN)在慢性阻塞性肺疾病(COPD)模型小鼠肺组织中的表达以及细辛脑对其表达的干预作用及其治疗意义。方法将40只BALB/C雌性小鼠随机分为对照组(A组)、COPD组(B组)、细辛脑组(C组)和富露施组(D组),每组10只。采用鼻腔滴入脂多糖(LPS)加熏香烟的方法建立COPD小鼠模型。运用HE染色对肺组织病变程度进行观察,评价COPD小鼠模型;Western blot方法检测肺组织中OPN的表达。计数血中白细胞;酶联免疫吸附试验(ELISA)法检测肺泡灌洗液中OPN的含量;免疫组化分析肺组织切片中OPN的表达。数据结果采用SPSS 17.0软件进行分析,两组均数比较采用两独立样本t检验,多组均数比较采用One-way ANOVA方差分析。结果 HE染色显示:COPD组与对照组相比,支气管管壁增厚,炎性细胞浸润明显,肺泡扩大甚至断裂。细辛脑组和富露施组支气管管壁厚度,炎性细胞浸润肺泡扩大程度较COPD组明显减轻;ELISA检测显示:与对照组相比,COPD组肺组织中的OPN表达明显增高(t=12.27,P=0.003),与COPD组相比,细辛脑和富露施组肺组织中的OPN表达明显减少(F=531.22,P<0.05)。血中白细胞计数:COPD组明显高于对照组(t=7.32,P<0.05),细辛脑组和富露施组白细胞计数明显少于COPD组(F=113.53,P=0.001);免疫组织化学的结果显示:与对照组比,COPD组OPN表达明显增加(t=5.67,P<0.05);与COPD组相比,细辛脑组和富露施组OPN的表达量明显减少(F=172.11,P=0.001)。结论 OPN可能是COPD疾病中重要的炎性介质,在气道炎症的发展和维持中起重要作用,细辛脑可以通过干扰OPN的生成,减弱COPD模型小鼠炎症的进展。     

慢性阻塞性肺疾病肺部感染的实验室检测指标分析

目的分析白细胞(WBC)、中性粒细胞百分比(NEUT%)和C-反应蛋白(CRP)测定在早期慢性阻塞性肺疾病(COPD)肺部感染诊断的临床使用价值及COPD肺部感染病原菌分布情况。方法选择186例临床诊断为COPD的住院患者为感染组,以60名健康体检者为对照组,比较两组WBC、NEUT%、CRP水平;以痰培养结果分为正常菌群组和有病原菌生长组,按培养出的病原菌分为革兰阳性(G~+)菌组和革兰阴性(G~-)菌组,对各组患者WBC和CRP水平进行统计分析,对这两项指标的灵敏度、特异性、阳性预测值进行比较。对痰培养阳性结果分布进行统计分析。结果感染组患者WBC、NEUT%和CRP水平均高于对照组,差异均有统计学意义(P0.05)。正常菌群组患者WBC和CRP水平与有病原菌生长组比较差异均无统计学意义(P0.05)。痰培养阳性中真菌86株,以白假丝酵母最多,占35.85%;细菌73株,G~+菌组患者WBC、NEUT%、CRP水平与G~-菌组比较差异均无统计学意义(P0.05)。结论 COPD患者WBC、NEUT%和CRP水平高于健康者,但由于WBC、NEUT%与CRP检测影响因素多,不能对COPD肺部感染进行早期诊断。     

多层螺旋CT定量研究慢性阻塞性肺疾病肺衰减值

目的 应用16层螺旋CT扫描观察慢性阻塞性肺疾病(COPD)患者肺衰减值与肺功能检查结果 的相关关系.方法 COPD患者共50例,均行16层螺旋CT检查和肺功能检查.通过直方图技术测量全肺平均衰减值(MLA)、小于-910 HU和小于-950 HU阈值的像素指数(PL910、PL950),评估MLA、PL910及PL950与肺功能检查结果 问的相关关系,并比较COPD 0～4级组间MLA、PL910及PL950的组间差异.结果 MLA、PL910及PL950与肺功能指标间均存在相关关系,与反映存在气流受限的指标FEV 1%FVC(%)相关关系最强,PL950与肺功能检查结果 间的相关关系较MLA、PL910强.PL950较MLA、PL910更能反映组间差异.结论 CT定量研究COPD肺衰减值可对患者肺实质改变进行全肺三维立体评估.PL950可作为CT定量评估COPD患者肺实质改变较敏感的指标.     

Double-blind comparison of tulobuterol and salbutamol in chronic obstructive pulmonary disease

A double-blind study compared tulobuterol (2 mg BID), a new beta 2-adrenergic agent, with salbutamol (2 mg TID) in 40 hospitalized men with chronic obstructive pulmonary disease. The study evaluated the bronchospasmolytic effects of the two drugs and their selectivity of action. Measurements and observations were made for six hours after the first oral dose, daily during nine days of continuous therapy, and for 12 hours after the final dose on the tenth day. Results show that the tulobuterol regimen produced a significant (P less than 0.01) improvement of the forced expiratory volume in one second equal to an increase of 25% above the pretreatment value, versus 16% with the salbutamol regimen. Cardiovascular effects appeared more rapidly with tulobuterol, but they stabilized to values lower than those observed with salbutamol. No clinically important adverse reactions were reported other than slight tremor, which was not objectionable.     

慢性阻塞性肺疾病患者与肺功能正常吸烟者CT肺实质灌注成像对照

目的 分析慢性阻塞性肺疾病（COPD）患者及肺功能正常吸烟者CT肺实质灌注图像的差异。方法 对63例COPD患者及20名肺功能正常吸烟者（对照组）行肺CTPI,将COPD患者分为轻度亚组（16例）、中度亚组（18例）、重度亚组（11例）和极重度亚组（18例）,在肺叶水平计算灌注缺损区与正常区CT值比值（R_HU）,比较各组体质量指数（BMI）、吸烟量及各肺叶R_HU的差异。结果 对照组BMI与重度、极重度COPD亚组比较,对照组吸烟量与极重度COPD亚组比较差异均有统计学意义（P=0.006、0.002、0.007）。同组各肺叶R_HU差异均无统计学意义（P均>0.05）。对照组右肺下叶R_HU与重度、极重度COPD亚组差异有统计学意义（P=0.03、0.02）,其他各肺叶R_HU各组差异均无统计学意义（P均>0.05）。对照组与各COPD亚组R_HU差异均有统计学意义（P均<0.05）;轻度与重度、与极重度COPD亚组,中度与极重度COPD亚组R_HU差异均有统计学意义（P=0.022、0.001、0.003）。结论 R_HU可区分COPD和肺功能正常吸烟者,有可能成为评估COPD严重程度的指标之一。