NLRP3/IL-1β/TGF-β1信号轴在矽肺肺纤维化大鼠模型中的表达及意义

目的探讨NLRP3/IL-1β/TGF-β1信号轴在矽肺肺纤维化大鼠模型中的表达情况及意义。方法选择健康SPF级Wistar雄性大鼠80只,随机分为4组,分别为高(100 mg/ml)、中(50 mg/ml)、低(25 mg/ml)浓度SiO2染尘组和正常对照组,每组20只。各组分别在SiO2染尘后7 d、14 d、28 d、56 d处死5只大鼠,观察肺组织肺泡炎程度及肺纤维化程度,采用酶联免疫吸附试验(ELISA)检测肺组织中IL-1β、IL-18、TGF-β1含量,Western Blot法检测大鼠肺组织中NLRP3、Caspase-1蛋白表达情况。结果与正常对照组比较,各染尘组大鼠7 d、14 d、28 d、56 d的肺泡炎评分、纤维化程度明显升高,差异均有统计学意义(P<0.01);与正常对照组比较,各染尘组大鼠7 d、14 d、28 d、56 d的IL-1β、IL-18、TGF-β1浓度明显升高(P<0.01);与正常对照组比较,各染尘组大鼠肺组织中NLRP3、Caspase-1蛋白表达在7 d、14 d、28 d、56 d均升高(P<0.01);低、中、高浓度SiO2染尘组内NLRP3、Caspase-1、IL-1β、IL-18和TGF-β1表达量在7 d、14 d和28 d间两两比较,差异均有统计学意义(P<0. 05),均呈随着染尘时间的增加而升高的时间-效应关系。结论NLRP3及其下游因子Caspase-1、IL-1β、IL-18、TGF-β1在矽肺肺纤维化大鼠模型肺组织中高表达,提示NLRP3/IL-1β/TGF-β1信号轴可能与矽肺肺纤维化有密切的关系,在矽肺形成过程中发挥了作用。     

早期联合用药对矽尘致大鼠肺纤维化的影响

目的：探讨早期用药对矽尘致大鼠肺纤维化的影响。方法采用ＳＤ大鼠,低剂量石英寺非暴露式气管注入染尘（２０ｍｇ／鼠）后３ｄ,在病变早期阶段开始给药,分别治疗２个月和５个月。疗效指标为肺湿重、肺胶元含量、肺总脂含量及肺内矽性病变分级。结果：以肺湿重、肺总脂为依据的综合疗效指标显示,各用药组都显著低于染尘对照组。肺内矽性病变分级亦有相应的差异。结论：早期联合用药对大鼠肺纤维化有一定阻断作用,其疗效优于各单     

304例矽肺患者的死因分析

目的探讨矽肺患者死因的特点。方法回顾性调查某钨矿304例矽肺患者的死因情况。结果矽肺全死因前3位为肺结核(54.3%)、肺心病(18.8%)和尘肺病(6.6%)。矽肺和肺结核病死率随着期别增加而升高(P<0.01),肺癌和其他癌症病死率随着期别增加而降低(P<0.05)。矽肺<60岁者病死率显著高于≥60岁者(P<0.01),肺心病和其他心血管病的病死率<60岁患者明显低于≥60岁者(P<0.01)。90年代矽肺病死率显著高于60、70年代(P<0.05),且肺结核病死率明显低于其他年代(P<0.01)。凿岩工矽肺、肺结核和肺心病的病死率明显高于其他工种(P<0.01)。结论矽肺主要死因为肺结核、肺心病和尘肺病。矽肺死因与矽肺期别、年龄、年代和工种有关。矽肺防治工作重点,应放在治疗和预防肺结核和肺心病。     

Association of angiotensin-1-converting enzyme gene variations with silicosis predisposition

Interactions between several genes and environmental factors occur in silicosis and other dust-mediated pulmonary fibrosis. It has been suggested that several genes play role in individual susceptibility to silicosis. The aim of this study was to determine the angiotensin-1-converting enzyme (ACE) gene (I/D) variations in patients with silicosis and healthy controls in Iranian Kurdish population. Forty-one male workers with silicosis and 41 healthy male controls were entered in the study. Polymerase chain reaction (PCR) method was carried out for allele and genotype typing. Our finding showed that the frequencies of D and I alleles were 0.65 and 0.35 in the silicotic patients compared to 0.52 and 0.48 in the controls. The frequencies of ACE D/D, D/I, and I/I genotypes were 15 (36.59%), 23 (56.1%), and 3 (7.31%) in patients, and 14 (34.15%), 15 (36.59%), and 12 (29.27%) in the controls, respectively. The results indicate that the frequency of ACE D/D+D/I genotypes were higher in the patients group (92.7% vs. 70.73%) (OR: 5.24, 95% CI: 1.35–20.30, P?=?0.01). Also, ACE I/I genotype frequency was lower in patients (7.32% vs. 29.27%) (OR: 0.19, 95% CI: 0.04–0.73, P?=?0.01). It can be concluded that ACE D/D and I/D genotypes may play a role in the susceptibility to silicosis; on the contrary, ACE I/I genotype may have protective effect.     

Radiographic silicosis and lung cancer risk among workers in Ontario

A case-control study, nested in a cohort of workers under surveillance for silicosis in 1979 or later, was undertaken to assess lung cancer risk in relation to the ILO coding scheme for the pneumoconioses. The subjects of this study are from the 41 matched quartets, consisting of one worker with silicosis and three age-matched controls, in which a lung cancer case was diagnosed. The odds ratio for lung cancer among subjects with ILO classification 1/0 or more, in comparison to subjects with category ≤ 0/1, was 3.27 (95%CI = 1.32–8.2). Adjustment of the radiographic risk for the effect of cumulative radon exposure had the effect of increasing the odds ratio for the association between ILO category ⩾1/0 and lung cancer. Although small smoking differences could account for the increased lung cancer odds ratio among workers with silicosis, the empirical evidence suggests that these smoking differences do not exist. It is concluded on the basis of two North American studies of silica exposed workers that radiographic silicosis is a marker for an increased risk of lung cancer. Am. J. Ind. Med. 34:244–251, 1998. © 1998 Wiley-Liss, Inc.     

矽肺矿工肺结核患病情况及结核菌素反应的调查分析

[目的]调查矽肺矿工中肺结核的流行情况,评估非结核矿工对结核菌素的反应性。[方法]病例对照设计,选择189例男性矽肺病人为病例,110例无矽肺的接尘矿工为对照。调查所有研究对象肺结核患病情况、职业史,并将接尘工龄划分为3组(<20年,20年-,30年-)。剔除肺结核患者59人,对其余矿工进行PPD皮肤试验。[结果]Ⅰ期矽肺组肺结核合并率为16.4%,Ⅱ期为29.0%,Ⅲ期为72.7%。对照组矿工中接尘工龄≥30年者肺结核患病率最高。Ⅱ期矽肺组结核菌素反应强阳性率为22.7%,高于对照组的8.3%。有明确的结核病接触史者,结核菌素反应阳性和强阳性率高于无结核病接触史者。[结论]随着矽肺期别升高,肺结核患病率增加。PPD皮肤试验可以作为矽肺患者合并肺结核的初筛手段之一。     

C/EBPβ在实验性矽肺大鼠肺中表达的研究

[目的]探讨转录因子CCAAT-增强子结合蛋白（CCAAT-Enhancer-Binding Protein-beta，C／EBP β）在矽肺建模大鼠中的表达及其意义。[方法]建立矽肺大鼠模型，运用免疫组织化学方法检测C／EBP β在30例染尘后不同阶段矽肺大鼠和10例正常大鼠肺组织中的表达，并对C／EBP β阳性细胞的类型、分布进行分析。[结果]C／EBP β主要表达于肺脏的上皮细胞及炎性细胞中。染尘后1—2周明显可见C／EBP β的核移位，C／EBP β在矽肺大鼠肺组织中表达较正常肺脏组织明显增强，且在染尘后36—64d的大鼠中其表达程度比在1—29d的大鼠中明显减弱，差异有显著性。[结论]C／EBP β在矽肺大鼠肺脏组织内的多种炎性细胞中明显表达，能客观反映免疫或炎症早期反应的程度，提示C／EBP β在矽结节产生和进展中可能发挥重要启动作用，其在早期矽肺大鼠肺脏组织上皮细胞中强阳性表达，提示上皮组织可能也是第一道抵御矽肺形成的防线。     

定群观察寿命表法研究结核对矽肺期望寿命的影响

采用定群观察寿命表法，即由定群寿命表法计算的死于尘肺及与尘肺有关并发症的观察时间别病死率，用现时寿命表法，研究并发肺结核对矽肺期望寿命的影响。研究对象来自某钨矿１９５６～１９９１年间定诊为矽肺结核及定诊矽肺后曾并发过肺结核的患者，并以该矿单纯矽肺为对照。结果显示：定诊矽肺后结核组最终死于尘肺及尘肺并发症的平均寿命为１４．１９年，非结核组为２３．８５年；矽肺患者因曾并发过肺结核损失平均寿命９．６６年，不并发肺结核可使矽肺的平均寿命（病程）增加６８．０８％。提示防止并发肺结核是尘肺第三级预防的重点。本文还对定群观察寿命表法的原理、应用进行讨论，并与部分文献用寿命表对尘肺期望寿命研究的方法结果进行比较。     

矽肺患者血清转化生长因子-β1和肿瘤坏死因子-α的变化

目的 观察矽尘接触者和矽肺患者及观察对象血清转化生长因子-β1(TGF-β1)和肿瘤坏死因子-α(TNF-α)水平,探讨TGF-β1、TNF-α在矽肺发生发展中的作用.方法 选择100名不接触粉尘的对照人群(对照组),200名接触矽尘1年以上的接尘工人(接尘组),32名矽尘作业观察对象(0+)(观察对照组)及130例矽肺患者(矽肺组),采用ELISA法检测其血清TGF-β1和TNF-α水平.结果 与对照组[(6.90±2.24)pg/ml]比较,接尘组、观察对象组和矽肺组TNF-α水平[(47.86±16.52)、(109.11±31.08)、(216.35±51.03)pg/ml]明显升高,差异有统计学意义(P＜0.01);与接尘组比较,观察对象组和矽肺组TNF-α水平明显升高,差异有统计学意义(P＜0.05,P＜0.01).与对照组[(23.28±12.24)pg/ml]和接尘组[(29.31±14.52)pg/ml]比较,观察对象组和矽肺组TGF-β1水平[(46.16±17.35)、(58.36±31.94)pg/ml]明显升高,差异有统计学意义(P＜0.05,P＜0.01).结论 TGF-β1和TNF-α在矽肺发生发展中有重要作用,检测外周血TGF-β1和TNF-α水平可应用于职业健康监护及矽肺的早期诊断.     

有机锗对大鼠实验性矽肺形成及脂质过氧化水平的影响

采用硫代巴比妥酸比色法和亚硝酸盐形成法，分别测定了实验性矽肺大鼠血清过氧化脂质（ＬＰＯ）及超氧化物歧化酶（ＳＯＤ）同工酶活力，同时观察了β羧乙基锗倍半氧化物（Ｇｅ－１３２）对实验性大鼠矽肺形成的阻断作用及对自由基代谢的影响。结果显示矽肺大鼠血清ＬＰＯ含量显著高于对照组，而血清总ＳＯＤ和ＣｕＺｎＳＯＤ活力显著下降。提示矽肺的发生可能与机体自由基代谢的失衡有关。使用Ｇｅ－１３２可显著提高大鼠机体的抗氧化能力，降低脂质过氧化作用，并可明显干预矽肺病变的形成。