被动吸烟对大鼠血清和肺组织中白细胞介素17表达的影响

目的观察被动吸烟和戒烟对大鼠被动吸烟模型血清和肺组织中白细胞介素(IL)-17变化的影响。方法选择健康雄性Wistar大鼠50只,随机分为5组,分别为正常对照组、被动吸烟4 w、8 w、12 w组和戒烟组。HE染色观察肺组织的病理改变,采用ELISA方法检测血清中IL-17含量,免疫组织化学染色方法观察肺组织中IL-17的表达。结果被动吸烟可导致肺组织炎症反应和肺气肿改变;被动吸烟组和戒烟组大鼠血清IL-17含量较正常对照组升高,肺组织中IL-17表达增强;随着被动吸烟时间的延长,血清中IL-17含量逐渐增加,肺组织中IL-17表达逐渐增加;戒烟组较被动吸烟12 w组血清IL-17含量降低,肺组织中IL-17表达减少。结论被动吸烟可引起肺部炎症,导致血清及肺组织IL-17表达增加,IL-17可能参与了吸烟相关性肺损伤的发生。     

戒烟对慢性阻塞性肺病模型大鼠肺组织病理及肺功能的影响

目的探讨戒烟对被动吸烟所致慢性阻塞性肺疾病(COPD)模型大鼠肺组织病理及肺功能变化的影响。方法选用Wistar雄性大鼠50只,随机分为对照组、COPD组、COPD戒烟1、2、3个月组,光镜下观察肺组织HE染色切片并进行病理学评分,检测各组大鼠肺功能。结果 COPD模型大鼠成功复制,可见气道壁炎性细胞浸润及杯状细胞增生、平滑肌和纤维组织明显增多,黏膜脱落、管腔狭窄,严重肺气肿形成。而在给大鼠戒烟后,上述病理变化不明显,仅见气道黏液细胞渗出在戒烟后第3个月内略有减少,但炎症细胞浸润仍在加重。而COPD模型大鼠在戒烟后肺功能指标仍有下降趋势,每分钟静息通气量(VE)指标在戒烟后第1、2、3个月内及呼吸峰流量(PEF)、第0.3秒用力呼气容积(FEV0.3)指标在戒烟后第2、3个月下降明显。肺功能在戒烟后下降速度仍有所减慢。结论戒烟不能使吸烟所致COPD病情立即缓解,但可延缓病程,故建议及早戒烟。     

香烟暴露及戒烟对大鼠支气管肺泡灌洗液白介素8、谷胱甘肽的影响

目的探讨香烟暴露及戒烟对大鼠肺部炎症的影响。方法 40只健康雄性SD大鼠随机分为对照组、吸烟组（1月、2月组）、戒烟组（1月、2月组）。每组各8只,吸烟组及戒烟组大鼠每天上下午在自制熏烟盒中各给予烟熏两次,吸烟组在分别吸烟1月、2月后取材;戒烟组在给予2月烟熏后停止,分别正常饲养1月、2月取材。活杀大鼠并通过肺组织HE染色观察气道炎症改变、收集支气管肺泡灌洗液（BALF）,用酶联免疫吸附实验（ELISA）检测支气管肺泡灌洗液（BALF）中白细胞介素-8（IL-8）、谷胱甘肽（GSH）含量表达。结果吸烟组及戒烟组BALF中炎症指标IL-8浓度明显高于正常组,GSH浓度明显低于正常组,但戒烟后IL-8,渐减低,GSH渐升高,但仍不能达到正常。结论吸烟可致肺部炎症加重氧化反应,戒烟可减轻上述反应。     

被动吸烟对大鼠血清肺表面活性蛋白A、D表达的影响

目的 通过烟熏法建立大鼠被动吸烟模型,观察被动吸烟和戒烟对血清肺表面活性蛋白A、D的影响,探讨被动吸烟肺损伤的发生机制.方法 选择健康雄性Wistar大鼠50只,随机分为5组,分别为正常对照组、被动吸烟4周组、被动吸烟8周组、被动吸烟12周组和戒烟组.HE染色观察肺组织的病理改变,采用酶联免疫吸附测定(ELISA)方法检测血清肺表面活性蛋白A、D含量.结果 被动吸烟可导致肺组织炎症反应和肺气肿改变;被动吸烟组和戒烟组大鼠血清肺表面活性蛋白A、D含量较正常对照组升高,随着被动吸烟时间的延长,血清肺表面活性蛋白A、D含量逐渐增加;戒烟组较被动吸烟12周组血清肺表面活性蛋白A、D含量降低.结论 被动吸烟可引起血清肺表面活性蛋白A、D表达增加,提示血清肺表面活性蛋白A、D可能参与了被动吸烟导致肺损伤的发病过程.     

戒烟对吸烟大鼠气道上皮细胞核因子κB、基质金属蛋白酶9及金属蛋白酶组织抑制物1表达的影响

目的 通过研究吸烟及戒烟大鼠气道上皮细胞核因子κB(NF-κB)、细胞基质金属蛋白酶9(MMP-9)及细胞金属蛋白酶组织抑制物1(TIMP-1)mRNA及蛋白质的表达水平,探讨吸烟及戒烟对慢性阻塞性肺疾病气道炎症和气道重塑的影响.方法 雄性Wistar大鼠24只,随机分为对照组、吸烟组和戒烟组,每组8只.分别采用原位杂交和免疫组织化学的方法检测各组大鼠气道上皮细胞中NF-κB、MMP-9及TIMP-1 mRNA及蛋白的表达水平.结果 ①与对照组(0.29±0.06,0.29±0.06)相比,吸烟组(0.45±0.04,0.41±0.03)、戒烟组(0.40±0.05,0.37±0.03)NF-κB mRNA和蛋白表达水平均增高(P值均＜0.05);与吸烟组相比,戒烟组NF-κB mRNA和蛋白表达水平降低(P值均＜0.05).②与对照组(0.30±0.06,0.30±0.06)相比,吸烟组(0.52±0.03,0.51±0.07)、戒烟组(0.38±0.03,0.33±0.02)MMP-9 mRNA和蛋白表达水平均增高(P值均＜0.05);与吸烟组相比,戒烟组MMP-9mRNA和蛋白表达水平均降低(P值均＜0.05).③与对照组(0.26±0.04,0.26±0.04)相比,吸烟组(0.49±0.05,0.37±0.03)、戒烟组(0.42±0.04,0.35±0.03)TIMP-1 mRNA和蛋白表达水平均增高(P值均＜0.05);与吸烟组相比,戒烟组TIMP-1 mRNA和蛋白表达水平降低(P值均＜0.05).④与对照组(1.00±0.02,1.00±0.02)相比,吸烟组(1.07±0.14,l.37±0.19)MMP-9/TIMP-1 mRNA和蛋白表达值大于1(P值均＜0.05),而戒烟组(0.92±0.13,0.94±0.10)MMP-9/TIMP-1 mRNA和蛋白表达值小于1(P值均＜0.05).⑤各组NF-κB和MMP-9的mRNA及蛋白的表达呈正相关(r值分别为0.87和0.66,P值均＜0.05).结论 吸烟大鼠气道上皮细胞NF-κB、MMP-9和TIMP-1 m-RNA及蛋白的表达水平升高,并且MMP-9/TIMP-1大于1,戒烟后NF-κB、MMP-9和TIMP-1的表达有所下降,且MMP-9/TIMP-1小于1,提示吸烟可以引起气道上皮的炎症和重塑,戒烟可以减轻气道炎症和重塑.     

粉防己碱抑制支气管哮喘小鼠肺组织核因子-κB和诱导型一氧化氮合酶的研究

目的：探讨粉防己碱对支气管哮喘(简称哮喘)小鼠肺组织核因子-κB(NF-κB)、诱导型一氧化氮合酶(iNOS)表达、气道炎症和气道高反应性的影响。方法将32只 SPF 级 BALB/c 小鼠随机分为正常组、哮喘组、地塞米松组(激素组)和粉防己碱组(Tet 组)。卵白蛋白(OVA)致敏和激发建立哮喘小鼠模型。末次激发24 h 后,肺功能仪测定小鼠气道阻力;HE 染色观察气道炎症细胞浸润;ELISA 检测血清总 IgE、OVA 特异性 IgE(OVA-sIgE)及 BALF 中 Th2细胞因子 IL-4和 IL-13水平;显微镜下计BALF 中细胞总数,瑞氏染色计嗜酸粒细胞分类计数;Western blot 检测肺组织 NF-κB 和 iNOS 蛋白表达水平。结果与正常组比较,哮喘组气道阻力、气道炎症浸润、BALF 炎症细胞总数和嗜酸粒细胞分类计数、血清总 IgE 和 OVA-sIgE、BALF 中 IL-4和 IL-13以及 NF-κB 和 iNOS 蛋白表达水平均显著增高(P <0.05);与哮喘组比较,激素和 Tet 干预组上述各项指标均显著降低(P <0.05)。结论粉防己碱可下调哮喘小鼠肺组织 NF-κB 和 iNOS 表达并抑制气道炎症和气道高反应性。     

姜黄素对COPD大鼠IL-1β和IL-17的影响

目的 探讨姜黄素干预对COPD大鼠IL-1β和IL-17水平的影响.方法 将雄性SD大鼠38只随机分为正常对照组、COPD模型组、姜黄素干预组和溶剂对照组,采用香烟烟熏加气管内注射脂多糖方法建立COPD大鼠模型,并按照分组情况对大鼠进行干预.干预结束后计数BALF中的炎症细胞总数、中性粒细胞和巨噬细胞数量,HE染色观察大鼠气道炎症及肺气肿程度,酶联免疫吸附测定检测血清和BALF中IL-1β、IL-17含量,实时荧光定量聚合酶链式反应检测肺组织中IL-1β、IL-17mRNA表达水平.结果 与正常对照组比较,COPD模型组BALF中炎症细胞总数、中性粒细胞和巨噬细胞数量均显著升高(P＜0.05);姜黄素干预组大鼠BALF中炎症细胞总数、中性粒细胞和巨噬细胞数量较COPD模型组降低(P＜0.05).组织病理学显示COPD模型组大鼠小气道周围大量炎症细胞聚集、肺泡腔扩张,姜黄素干预可减轻小气道周围炎症细胞聚集及肺泡腔扩张.与正常对照组相比,COPD模型组大鼠血清和BALF中IL-1β、IL-17含量升高,肺组织中IL-1β、IL-17mRNA表达水平上调,差异有统计学意义(P＜0.05).姜黄素干预后COPD大鼠血清和BALF中IL-1β、IL-17含量下降,肺组织中IL-1β、IL-17mRNA表达水平降低,与COPD模型组比较差异有统计学意义(P＜0.05).结论 姜黄素对COPD具有保护作用,其机制可能与抑制IL-1β、IL-17炎症因子释放有关.     

孟鲁司特钠对哮喘大鼠肺组织、脾脏、胸腺NF-κB mRNA表达的影响及病理变化的研究

目的观察白三烯受体拮抗剂孟鲁司特钠对哮喘大鼠肺组织、脾脏、胸腺NF-κB mRNA的表达及病理变化的影响。方法建立哮喘大鼠模型后,将动物随机分成三组,正常对照组、哮喘组、孟鲁司特钠组。干预后处死动物,用原位杂交法检测肺组织、脾脏、胸腺淋巴细胞中NF-κB mRNA的表达及光镜观察肺组织、脾脏的病理变化。结果与正常对照组比较,哮喘组大鼠肺组织气道周围炎症明显,肺泡隔增宽。脾脏白髓淋巴细胞区中度增生。孟鲁司特组肺组织气道周围炎症减轻,肺泡隔增宽有所减轻,脾脏白髓淋巴细胞区轻-中度增生。哮喘组大鼠肺组织、脾脏、胸腺淋巴细胞中NF-κB mRNA的表达增加（P〈0.05）。孟鲁司特钠组大鼠肺组织、脾脏、胸腺淋巴细胞中NF-κB mRNA的表达受抑（P〈0.05）。结论孟鲁司特钠在支气管哮喘的发病机制中有一定的抗炎作用。     

地塞米松对哮喘大鼠气道重建、肥大细胞及IL-10的影响

目的观察地塞米松对哮喘大鼠模型气道重建和肺组织肥大细胞、IL-10的影响,探讨地塞米松在气道炎症和气道重塑中的作用机制,为临床治疗提供依据。方法采用卵白蛋白（OVA）腹腔注射致敏和雾化吸入激发建立哮喘大鼠模型,30只SD大鼠随机分为3组,正常对照组（A）、哮喘组（B）、地塞米松干预组（C）,每组10只。对肺组织切片行苏木精-伊红（HE）染色观察气道重塑情况。采用免疫组化和图像分析技术测定各组大鼠肺组织肥大细胞、IL-10的表达。结果哮喘组动物出现管壁增厚、平滑肌增生、黏液分泌增加等气道重塑的特征性改变,免疫组化染色显示气道各层细胞及炎性细胞均有IL-10表达减少。地塞米松干预组与哮喘组比较,炎症反应轻微,平滑肌增生、黏液分泌不明显,免疫组化染色显示各类细胞IL-10表达增高,与对照组比较差异有统计学意义。结论长期吸入变应原可导致气道重塑,肥大细胞、IL-10在气道重塑中发挥重要作用,地塞米松可通过抑制肥大细胞脱颗粒、增加IL-10表达发挥抑制炎症作用,进而缓解哮喘大鼠气道重塑的发生。     

IL-10对急性坏死性胰腺炎大鼠NF-кB及IL-12水平的影响

目的 观察白介素10(IL-10)对ANP大鼠NF-кB和IL-12表达的影响,探讨IL-10的作用机制.方法 将92只SD大鼠按随机分组法分为对照组、ANP组和IL-10干预组.采用3次腹腔注射左旋精氨酸(1.0 mg/g体重)的方法制备ANP模型.对照组腹腔注射等量生理盐水.IL-10组在制模后2、5、8 h分别于腹腔内注射IL-10 10 000U.制模后4、12、24、36 h分批处死动物,观察血清淀粉酶、IL-12及胰腺组织NF-кB水平的变化.结果 制模后24 h点IL-10组胰腺病理分值为4.75±1.75,胰腺NF-кB含量为(112.89±34.48)μg/ml,血清淀粉酶含量为(1 481.13±336.48)U/L,血清IL-12水平为(81.31±17.23)pg/ml,均明显低于同时点ANP组大鼠(P＜0.05或P＜0.01).NF-кB和IL-12呈正相关(r=0.494,P＜0.01),两者与胰腺病理分值也呈正相关(r=0.447和r=0.603,P＜0.01).结论 IL-10对ANP有一定的治疗作用,其机能可能通过抑制NF-кB途径而抑制ANP的炎症反应.     

Secondhand smoking and smoking bans

Secondhand smoking (SHS), also known as passive smoking or environmental tobacco smoke, is a serious threat to public health. Exposure to SHS is a significant risk factor for lung cancer, respiratory diseases, stroke, and coronary heart disease (CHD) among nonsmokers and is responsible for about 49,000 deaths per year in the United States. In an effort to protect nonsmokers from exposure to SHS, several countries have implemented smoking bans. These bans have been shown not only to reduce exposure to SHS but also to decrease the prevalence and intensity of active smoking. Smoking bans have also been associated with both short-term (< 12 months) and long-term (> 12 months) reductions in hospital admissions for CHD following the implementation of smoking bans. For studies reporting short-term follow-up, this reduction ranged from 11% to 17%, whereas the drop in CHD-related hospital admissions from studies with longer-term follow-up ranged from 8% to 47%. Higher reductions were reported among nonsmokers and young people. Smoking bans are effective in reducing exposure to SHS and could have immediate and long-term benefits for cardiovascular health. Smoking bans are a very effective public health measure to prevent CHD.     

The control of smoking: smoking rate in designated smoking and no-smoking areas

Unobtrusive measurements were taken over a 5-day period at three hospital areas designated as smoking permitted and three designated as no-smoking. A surprisingly high degree of compliance was observed in reported patient complaints or criticisms in regard to the controlled-smoking policy. The practical advantages of a comprehensive, hospital-wide sign program designating smoking and no-smoking areas are discussed.     

Attitudes toward smoking and smoking rate: implications for smoking discouragement

Attitudes toward smoking were measured among nonsmokers and five levels of smokers (light to heavy). Of 13 attitude items, a relationship between attitudes and number of cigarettes smoked was found to exist in five, three of which dealt with smoking as a health risk. The results suggest that the more cigarettes a person smokes, the greater the likelihood of denial of the health hazards associated with smoking.     

Inattentiveness, parental smoking and adolescent smoking initiation

AIMS: To examine how adolescents' inattentive behaviour, together with parental smoking patterns, predicts smoking initiation by age 14. DESIGN, SETTINGS: A prospective, longitudinal study: baseline at ages 11-12, follow-up at age 14. A population-based sample of Finnish twins, born 1983-1987, with parents and classroom teachers as additional informants. Two groups were formed, allocating the co-twins of each family into separate groups: the study sample and a replication sample. PARTICIPANTS: Twin individuals (n = 4552), aged 11-12 at baseline and 14 (average 14.04 years) at follow-up. MEASUREMENTS: At baseline, inattentiveness was assessed with the Multidimensional Peer Nomination Inventory (MPNI, Teacher Form) and parental smoking with individual questionnaires completed by each twins' parents; at the age 14 follow-up, adolescent smoking was assessed with a self-report questionnaire. FINDINGS: At age 14, 57% reported never having smoked, 34% had experimented with cigarettes and 9% were current smokers. Inattentiveness and parental smoking additively predicted both experimental and current smoking in adolescence. The effects were independent of each other. CONCLUSIONS: The risk related to inattentiveness itself is high, but in combination with the effects of parental smoking, the probability of current smoking can rise as high as 38%, compared with 5% without these two risk factors. For prevention purposes, parental commitment to non-smoking should be emphasized.     

Quitting smoking

Four factors which influence smoking treatment outcome are identified: environmental variables, client characteristics, process variables, and specific treatment approaches. Important environmental factors are stress and social support. Of client characteristics, sex is the best predictor of treatment success. Men are more likely to quit and maintain abstinence than women. However, the majority of women alter their smoking habits during pregnancy. Low-income persons and ethnic minorities are underrepresented among subjects in treatment studies and have larger percentages of smokers in the population at large. Extraverted smokers are more likely to begin to smoke and have difficulty quitting. Also, the more anxious, poorly adjusted smoker has more trouble quitting than the less troubled smoker. The higher the client's sense of self-efficacy, the better the chance of that person entering treatment and doing well. Furthermore, smokers who take in lower levels of nicotine are more successful at quitting. Many process questions are suggested. Few have been approached empirically. The effectiveness of ex-smokers as therapists in smoking cessation programs has not been systematically investigated, even though the smoking history of therapists is a question frequently asked by clients. We suggest that the skill and empathy of group leaders is more important than smoking history. Smoking therapists should be aware of nonspecific treatment factors such as positive expectations, social reinforcement, and self-disclosure which may have a powerful influence on the efficacy of smoking treatment. Specific treatment approaches were classified into three categories: low-contact approaches, including educational, self-help, and minimal treatment approaches; psychological treatments; and pharmacological treatment. Education, self-help, and minimal treatment approaches are thought to be accretively effective when the large size of the audience is considered. Also, innovative treatments which address the influence of social support systems and physiological addition are promising treatments for individuals requiring a structured or intensive method of quitting.     

Quitting smoking

OBJECTIVE: To describe why medical patients quit smoking and the methods they use. DESIGN: Cross-sectional and prospective cohort design. Patient smokers were enrolled in a study of physician counseling about smoking. One year later, 2,581 of the patients were asked about quit attempts and methods used. Of those, 245 former smokers whose quitting had been biologically validated were interviewed about why and how they had quit. SETTING: Offices of internists and family practitioners in private practice and a health maintenance organization. SUBJECTS: Consecutive sample of ambulatory patients who smoked. MEASUREMENTS AND MAIN RESULTS: Baseline questionnaires included demographic data, smoking history, and symptoms and diagnoses related to smoking. After one year, subjects were interviewed about smoking status and methods used in attempting to quit. Cessation was confirmed by biochemical testing. Those who had quit were asked about reasons for quitting. Seventy-seven percent of successful quitters gave health-related reasons for quitting and the quitters ranked "harmful to health" as the most important reason for quitting. In a multivariate analysis, those who had a college education, who had social pressures to quit, and who had greater confidence in being able to quit were more likely to have quit smoking one year later, while those who smoked their first cigarette within 15 minutes of awakening and who had more diagnoses related to smoking were less likely to have quit smoking one year later. Participation in a treatment program and having been counseled by a physician or nurse practitioner were positively related to successful quitting, while use of filters or mouthpieces was negatively related. CONCLUSIONS: Concerns about health are the most common reason patients give for quitting, and addiction is the most important barrier to quitting. Education, social pressure, provider advice, and formal programs, but not over-the-counter devices, appear to increase the chances that smokers will quit.     

Cigarette smoking

Received from the Division of General Medicine and Primary Care, University of Massachusetts Health Sciences Center, Worcester, Massachusetts.     

Statistical analysis of daily smoking status in smoking cessation clinical trials

Aims Smoking cessation trials generally record information on daily smoking behavior, but base analyses on measures of smoking status at the end of treatment (EOT). We present an alternative approach that analyzes the entire sequence of daily smoking status observations. Methods We analyzed daily abstinence data from a smoking cessation trial, using two longitudinal logistic regression methods: a mixed‐effects (ME) model and a generalized estimating equations (GEE) model. We compared results to a standard analysis that takes abstinence status at EOT as outcome. We evaluated time‐varying covariates (smoking history and time‐varying drug effect) in the longitudinal analysis and compared ME and GEE approaches. Results We observed some differences in the estimated treatment effect odds ratios across models, with narrower confidence intervals under the longitudinal models. GEE yields similar results to ME when only baseline factors appear in the model, but gives biased results when one includes time‐varying covariates. The longitudinal models indicate that the quit probability declines and the drug effect varies over time. Both the previous day's smoking status and recent smoking history predict quit probability, independently of the drug effect. Conclusion When analysing outcomes of studies from smoking cessation interventions, longitudinal models with multiple outcome data points, rather than just end of treatment, can makes efficient use of the data and incorporate time‐varying covariates. The generalized estimating equations approach should be avoided when using time‐varying predictors.