不同变质期煤尘致病作用的实验研究

在广西四个不同煤矿矿井下回采工作面采集新鲜无烟煤、烟煤及褐煤，制成煤尘后对Ｗｉｓｔａｒ大鼠进行非暴露式一次染尘。染尘４５天及９０天时宰杀大鼠进行实验研究。结果：大鼠肺冲洗液中脂质含量、鼠肺干、湿重及全肺胶原含量，石英组（阳性对照）大于煤尘组，煤尘组大于生理盐水组（阴性对照），差异有显著性意义（Ｐ＜０．０１）；煤尘组间的差异与其变质程度的高低无关。提示石英尘的致病性比煤尘强，煤尘致病性的强弱与其变质程度的高低无相关关系。     

不同品位煤尘对大鼠肺冲洗液中脂质含量的影响

目的 观察不同品位煤尘对大鼠肺冲洗液中脂质含量的影响。方法 实验分为９组，染尘时间分别为３０、９０、１８０和３６０天。结果 各煤尘组大鼠肺冲洗液中脂质含量高于同期对照组，但又都低于同期石英组。煤尘组间的差异与煤变质程度的高低无关，与煤尘中游离二氧化矽含量高低有关。结论 煤尘的致病性强弱与煤尘中ＳｉＯ２含量高低有关。     

广西不同煤质和围岩粉尘对大鼠肺纤维化病变的研究

目的：探讨不同煤种煤尘致病性的特点,确定影响煤尘致病性的主要因素。方法：采用广西烟煤、无烟煤和褐煤不同煤种粉尘制作大鼠尘肺模型,从生化指标来探讨不同的煤种粉尘与尘肺的发病关系。结果：染尘大鼠肺冲洗液中酸性磷酸酶、乳酸脱氢酶,肺组织中脂质过氧化物、胶原蛋白含量均为石英组最高,其次依次是烟煤组、无烟煤组、褐煤组,最低为正常对照组,结果差异有显著性（P＜0．01）。结论：围岩煤尘具有一定的致病性,但较石英弱,其致病性强弱与煤质优劣无关,与围岩煤尘中游离二氧化矽的含量高低有一定关系。     

吸入含矽粉尘和煤尘在大鼠肺中滞留的比较研究

以大鼠动式吸入染尘方法吸入含矽尘和煤尘２周。用甲酸消化法测定大鼠肺和纵膈淋巴结中的粉尘含量。结果发现在染尘结束后的第３天，煤尘组大鼠肺中的粉尘含量高于矽尘组；９０天后则矽尘组大鼠肺中的粉尘含量高于煤尘组。提示含矽粉尘在肺中滞留较煤尘持久，因而可对肺产生较为严重的损伤。结果也同时证实淋巴系统是肺内粉尘转移的一条重要途径。     

矽尘对大鼠肺表面活性蛋白影响的研究

目的 探讨不同矽尘暴露时间对于大鼠肺表面活性蛋白(SP)A、B、C、D的影响,为矽肺的早期诊断和临床治疗提供理论依据.方法 将60只大鼠随机分为染尘组和相应对照组,每组30只.染尘组大鼠经气管灌注50 mg/ml的粉尘1 ml,左右两肺各0.5 ml;对照组灌注等量的生理盐水.在染尘后第3、7、14、21、28天分别获取血清和支气管肺泡灌洗液(BALF),应用酶联免疫法(ELISA)检测大鼠血 清和BALF中SP-A、SP-B、SP-C、SP-D的含量.同时检测肺组织中总抗氧化能力(T-AOC)和羟脯氨酸(HYP)的含量,对肺组织进行HE染色观察病理变化.结果 与对照组比较,3、14、21、28 d染尘组大鼠BALF中SP-A含量及各时点染尘组大鼠BALF中SP-D含量均明显降低,差异均有统计学意义(P＜0.05);与对照组比较,7、14、21、28 d染尘组大鼠BALF中SP-B含量及14、21、28 d染尘组大鼠BALF中SP-C含量明显升高,差异有统计学意义(P＜0.05).与对照组比较,14、21、28 d染尘组大鼠血清中SP-A含量及7、14、21d染尘组大鼠血清中SP-B含量及7、14、21、28 d染尘组大鼠血清中SP-C含量明显增加,差异均有统计学意义(P＜0.05),且随染矽尘时间的延长,血清中SP-C含量呈增加趋势,有时间-效应关系(r=0.618,P=0.042).与对照组比较,7、14、21、28 d染尘组大鼠血清中SP-D含量降低,差异有统计学意义(P＜0.05);随着染尘时间的增加,血清中SP-D含量呈下降的趋势,有时间-效应关系(r=-0.731,P=0.016).与对照组比较,3、7、14、21、28 d染尘组大鼠肺组织中HYP含量升高,7、14、21、28 d染尘组大鼠肺组织中T-AOC含量下降,差异均有统计学意义(P＜0.05).染尘大鼠BALF中SP-C的含量与肺组织中HYP呈正相关(r=0.803,P=0.045);BALL中SP-D的含量与肺组织中HYP呈负相关(r=-0.867,P=0.033).BALF中SP-A、SP-B含量与肺组织中HYP无相关(r=0.416,P=0.28;r=0.592,P=0.071).BALF与血清中SP-D含量的均呈下降趋势,呈正相关(r=0.870,P=0.034).BALF与血清中SP-C含量均增加呈正相关(r=0.539,P=0.046).染尘组大鼠肺组织病理观察可见,肺泡间隔逐渐增厚,尘细胞浸润,有少量胶原纤维分布,至28 d时,出现尘细胞结节.结论 矽尘导致大鼠BALF中SP含量改变,血清中SP-C、SP-D的水平可作为矽肺早期效应标志物.     

红茶菌制剂对染尘大鼠肺干重及游离二氧化硅含量的影响

目的通过给予含与不含中草药的红茶菌制剂进行喷雾治疗,研究其对染尘大鼠全肺干重及肺游离二氧化硅含量的影响。方法取SD大鼠24只,随机分为红茶菌复合制剂组、红茶菌单纯制剂组、阳性对照组、阴性对照组(不染尘)。用标准石英粉尘配成的矽尘混悬液注入大鼠气管,复制矽肺动物模型。染尘后第4天开始对2个红茶菌制剂组进行喷雾给药,给药4周后处死动物,进行全肺干重及肺游离二氧化硅含量测定。结果红茶菌单纯制剂组全肺干重和游离二氧化硅含量均为最高,与阳性对照组比较差异无统计学意义(P0.05);红茶菌复合制剂组肺游离二氧化硅含量值低于其他各染矽尘组,差异有统计学意义(P0.05)。结论红茶菌复合制剂组能促进二氧化硅粉尘从大鼠肺部组织排出,具有一定的生物排尘功能。红茶菌单纯制剂对大鼠的排尘效果不明显。     

坎地沙坦对染尘大鼠肺纤维化的影响

目的 观察坎地沙坦对染尘大鼠矽肺形成过程中血管紧张素Ⅱ(AngⅡ)、肺纤维化及细胞因子的影响.方法 将Wistar大鼠随机分为模型组、干预组、对照组,每组32只.干预组每天灌胃坎地沙坦10 mg/kg,模型组和对照组同法给予等量生理盐水;灌胃1周后,模型组和干预组水合氯醛腹腔注射麻醉,将0.5 ml矽尘混悬液(浓度为50 mg/ml)缓慢注入气管,对照组大鼠气管内注入0.5 ml灭菌生理盐水.染尘后第2天,各组大鼠恢复先前的处理后第3、7、14、28天各处死大鼠8只.计算肺脏系数并进行肺组织HE及Masson染色观察;用免疫组化方法测定肺组织血管紧张素转化酶(ACE)表达水平;用ELISA测定肺泡灌洗液中转化生长因子β1(TGF-β1)及AngⅡ含量.结果 干预组大鼠第3、7、14、28天肺泡炎症和纤维化程度均较模型组明显减轻,干预组大鼠肺脏系数明显低于模型组,差异有统计学意义(P＜0.01).与对照组比较,模型组和干预组肺泡灌洗液中TGF-β1和Ang Ⅱ含量均明显升高,差异有统计学意义(P＜0.01);与模型组比较,干预组肺泡灌洗液中TGF-β1和Ang Ⅱ含量均明显降低,差异有统计学意义(P＜0.01).模型组和干预组肺组织ACE表达明显高于对照组,干预组肺组织ACE表达明显低于模型组,差异均有统计学意义(P＜0.01).结论 早期使用坎地沙坦干预能够明显减轻染尘大鼠的肺组织炎症和肺纤维化程度,降低肺泡灌洗液中的TGF-β1和AngⅡ含量,下调肺组织中ACE表达.     

咯萘啶对大白鼠矽肺疗效研究

咯萘啶的水溶液经口灌胃给药,大鼠染尘3天后即给药治疗,一个月内肺组织病变基本是间质性肺炎、尘细胞浸润,而此时尘肺对照组大鼠肺组织已出现纤维细胞性结节。相应的肺门淋巴结的硬度、大小和肺湿重T/C比值(均小于0.75)与肺组织纤维化程度相一致。染尘1个月后给药治疗,高低剂量组的肺湿重T/C比值均远大于0.75,肺门淋巴结变化和肺纤维化程度与尘肺对照组相比没有明显区别。     

槲皮素干预二氧化硅粉尘致肺纤维化大鼠的实验研究

目的观察槲皮素对二氧化硅粉尘所致肺纤维化的影响。方法选取48只雄性健康成年SPF级SD大鼠为研究对象,随机分为6组(对照组,槲皮素干预组,染尘7天、14天、21天和28天组)。对照组大鼠经气管注入无菌生理盐水1 ml,染尘组和槲皮素干预组大鼠注入50 mg/ml二氧化硅混悬液1 ml,预防组以50 mg/kg的槲皮素每天灌胃干预治疗,取肺组织进行HE染色,确定肺泡炎和肺纤维化程度,并检测肺组织中羟脯氨酸(HYP)含量以及过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)活性。结果对照组大鼠肺组织结构基本正常;染尘组大鼠第7天时肺泡腔内可见大量炎性细胞浸润;14天时肺泡间隔内成纤维细胞显著增多,肺泡结构破坏;21天时大量巨噬细胞聚集形成细胞性结节且结节内有少量的胶原纤维;28天时肺纤维化程度进一步加重,形成广泛纤维化。随染毒时间的增加,肺组织中HYP的表达量逐渐升高,CAT及GSH-Px的活性逐渐降低;加入槲皮素后肺组织中HYP的表达量降低,CAT及GSH-Px的活性升高,差异具有显著性(P0.05)。结论槲皮素对矽尘所致的肺纤维化有一定的预防作用。     

银杏叶提取物改善肺内淋巴转运对大鼠矽肺病程的影响

[目的]通过银杏叶提取物改善矽肺大鼠肺内淋巴转运,探讨其对矽肺病程的影响。[方法]Wistar雄性大鼠随机分为正常对照组、处理对照组、染尘组及处理组,每组按不同采样时间又分为第7天、第14天、第28天、第42天、第56天5个亚组,每组6只。染尘组及处理组大鼠以非气管暴露法气管内注入1 mL二氧化硅混悬液(50 mg/mL);处理组每日经食道灌注银杏叶提取物混悬液(100 mg/kg);正常对照组灌入等剂量生理盐水,处理对照组灌入等剂量银杏叶提取物混悬液。分别检测肺组织中羟脯氨酸、血管内皮生长因子受体-3(VEGFR-3)及淋巴液中硅元素水平。[结果]染尘组和处理组与对照组相比,大鼠染尘后VEGFR-3及淋巴液硅元素水平均在时间上呈先增高后降低趋势,于第14天达高峰;羟脯氨酸含量持续增加。与染尘组比较,处理组第28~56天VEGFR-3水平升高(P0.05),淋巴液硅元素水平在第7~28天亦升高(P0.05);各时间点处理组羟脯氨酸含量均低于染尘组(P0.05)。Pearson相关性分析显示,染尘组及处理组淋巴液硅元素与肺组织VEGFR-3均呈正相关(r=0.651,P0.01;r=0.613,P0.01);硅元素与肺组织羟脯氨酸均呈负相关(r=-0.786,P0.01;r=-0.899,P0.01)。[结论]银杏叶提取物可能通过促进淋巴循环,加快肺内二氧化硅的排除。     

Pulmonary Effects of Tobacco and Related Substances

Pulmonary burdens of quartz dust and bituminous coal dust, respectively, were imposed upon rats and hamsters by inhalation and intratracheal injection before and after production of papain- induced emphysema. Quantitation was performed of the pulmonary content of silica, hydroxyproline, and lipids of the animals burdened with quartz dust and of the pulmonary dust content only of the animals burdened with coal dust. There were statistically significant reductions in mean silica content as well as mean coal dust content of emphysematous lungs in all four groups of hamsters. In rats, whereas the mean pulmonary dust content was lower in emphysematous animals than in nonemphysematous controls, this difference was statistically significant in only two of the four groups. Improved dust clearance is believed to be a major factor in the reduction of dust content of emphysematous lungs.     

Lung oxidative response after acute coal dust exposure

Coal dust exposure can induce an acute alveolar and interstitial inflammation that can lead to chronic pulmonary diseases. The objective of this study was to describe the acute and later effects of acute coal dust exposure in lung parenchyma and the involvement of reactive oxygen species in coal dust effects. Forty-eight male Wistar rats (200-250 mg) were separated into four groups: 48 h, 7 days, 30 days, and 60 days after coal dust instillation. Gross mineral coal dust (3 mg/0.5 mL saline) was administered directly in the lungs of the treatment group by intratracheal instillation. Control animals received only saline solution (0.5 mL). Lipid peroxidation was determined by the quantity of thiobarbituric acid-reactive species (TBARS), oxidative damage to protein was obtained by the determination of carbonyl groups, the total radical-trapping antioxidant parameter (TRAP) was estimated by luminol chemoluminescence emission, catalase activity was measured by the rate of decrease in hydrogen peroxide, and superoxide dismutase activity was assayed by the inhibition of adrenaline autooxidation. Histological evaluation of coal dust-treated rats demonstrated an inflammatory infiltration after 48 h of the exposure. Initially, this was a cellular infiltration suggestive of lymphocyte infiltration with lymphoid hyperplasia that remained until 7 days after induction. This initial response was followed by a chronic inflammatory infiltration characterized by aggregates of macrophages 30 days after induction. This inflammatory response tended to resolve 60 days after induction, being similar to that of control animals. During both the acute and chronic phases of lung inflammation we observed a decrease in the TRAP in the lung of coal dust-exposed animals compared to that in control animals. We also observed an activation of superoxide dismutase 60 days after coal dust exposition. TBARS were increased 60 days after coal dust exposure and protein carbonyl groups increased at all times after coal dust exposure (48 h, 7 days, 30 days, and 60 days). These data suggested a biphasic inflammatory response and the involvement of oxidative damage in coal dust-induced lung damage.     

The response of rat alveolar macrophages to chronic inhalation of coal dust and/or diesel exhaust

The use of diesel-powered equipment in underground mines has raised questions regarding possible synergistic effects of coal dust and diesel emissions. Therefore, the effects of chronic exposure of rats to coal dust and/or diesel exhaust on various properties of alveolar macrophages were investigated. Inhalation exposure of rats was 7 hr/day, 5 days/week for 2 years. Exposure groups were: filtered air controls, 2 mg/m3 coal dust, 2 mg/m3 diesel particulate, and 1 mg/m3 coal dust plus 1 mg/m3 diesel exhaust. Exposure to coal dust and/or diesel exhaust had little effect on oxygen consumption, membrane integrity, lysosomal enzyme activity, or protein content of alveolar macrophages. However, exposure to coal dust increased macrophage yield, enhanced chemiluminescence, and increased the activity of the cell membrane (i.e., increased cellular spreading and surface ruffling). In contrast, diesel emissions depressed chemiluminescence and decreased the ruffling of the cell membrane. Therefore, the data suggest that exposure to coal dust and/or diesel exhaust does not affect the viability of alveolar macrophages. However, coal dust may activate alveolar macrophages while diesel emissions may depress the phagocytic activity of these cells. The combination of exposures to coal dust and diesel exhaust results in a phagocytic activity which is an average of the effects of separate exposures.     

褐煤尘细胞毒性和致纤维化作用

为了评价褐煤尘的细胞毒性及致纤维化作用，对２个褐煤矿的煤尘成分、体外细胞毒性、体内致肺损伤作用进行了研究。甲矿煤尘游离ＳｉＯ２含量为３．４％，乙矿煤尘为１．５％。培养液中加入褐煤尘后肺巨噬细胞存活率明显降低，乳酸脱氢酶（ＬＤＨ）和酸性磷酸酶（ＡＣＰ）活力明显增高。乙矿煤尘组细胞存活率明显低于甲矿煤尘组，ＬＤＨ明显高于甲矿煤尘组。染褐煤尘大鼠肺体积、湿重、干重和胶原蛋白含量增加，病理检查可见到煤尘灶、肺气肿、网状纤维和胶原纤维轻度增生。结果表明：褐煤尘具有细胞毒性和轻度致纤维化作用，乙矿煤尘细胞毒性和致纤维化作用均高于甲矿煤尘，用煤尘中元素含量解释煤尘毒性与以往的研究结果不尽相同。     

煤矿工煤肺患病率、煤尘实验研究及其影响因素的分析

本文选择了均属烟煤的大同煤矿和汾西煤矿为研究对象。比较了两矿煤肺的患病率,并取煤尘进行溶血试验,细胞毒性实验及大鼠染尘实验,均表明大同煤较汾西煤的致纤维化作用强。大同媒中多种金属元素(Ni、Pb、Cu、Co)及挥发份均非常显著地高于汾西煤。为此将两种煤去掉挥发份后,再进行实验,结果表明,处理后的两种煤均较未处理的煤对细胞的毒性减低。认为挥发份在煤尘致纤维化作用中有一定影响,但并不是唯一的因素。