转化生长因子-β1、肿瘤坏死因子-α、可溶性白细胞介素2受体及T细胞亚群与肺尘埃沉着病分期和肺功能的关系

Relationship of TGF-β1, TNF-α, sIL-2R and T cell subsets and pneumoconiosis stage and pulmonary function

目的 探讨外周血和支气管肺泡灌洗液（BALF）中转化生长因子-β1 （TGF-β1）、肿瘤坏死因子-α（TNF-α）、可溶性白细胞介素2受体（sIL-2R）水平及外周血T细胞亚群与肺尘埃沉着病（简称尘肺）分期和肺功能的关系.方法 选择2010年4月～2012年7月在郑州煤炭工业集团有限责任公司总医院治疗的尘肺患者68例为尘肺组,另选择同期接尘组和对照组各35例,采用酶联免疫吸附法检测三组外周血及尘肺组BALF中TGF-β1、TNF-α、sIL-2R水平,采用流式细胞技术检测三组外周血T细胞亚群并检测尘肺组肺功能.结果 尘肺组、接尘组和对照组血清TGF-β1和sIL-2R水平差异有统计学意义（P＜0.05）,尘肺组不同分期血清TGF-β1、TNF-α、sIL-2R水平差异有统计学意义（P＜0.05）,不同尘肺分期血清TGF-β1、sIL-2R水平均显著高于接尘组和对照组（P＜0.05）,Ⅱ、Ⅲ期血清TNF-α水平显著低于接尘组和对照组（P＜ 0.05）；血清TGF-β1、sIL-2R水平与尘肺分期呈正相关（P＜0.05）,血清TNF-α水平与尘肺分期呈负相关（P＜0.05）.不同分期尘肺患者BALF中TGF-β1、TNF-α、sIL-2R水平差异均有统计学意义（P＜0.05）,尘肺患者BALF中TGF-β1、TNF-α水平与分期无显著相关（P＞0.05）,尘肺患者BALF中sIL-2R水平与分期呈正相关（P＜0.05）.尘肺组、接尘组和对照组外周血CD8＋及CD4＋/CD8＋差异有统计学意义（P＜0.05）,不同尘肺分期外周血CD4＋、CD8＋及CD4＋/CD8＋差异有统计学意义（P＜0.05）,Ⅱ、Ⅲ期尘肺外周血CD4＋及CD4＋/CD8＋显著低于接尘组和对照组（P＜0.05）,Ⅰ、Ⅲ期尘肺外周血CD8＋百分百显著高于接尘组和对照组（P＜0.05）；外周血CD4＋、CD8＋百分百与尘肺分期无显著相关（P＞0.05）,而CD4＋/CD8＋与尘肺分期呈负相关（P＜0.05）.外周血TGF-β1水平与FVC、FEV1/FVC及DLCO呈负相关,sIL-2R与FVC、DLCO呈负相关,TNF-α水平与肺功能无显著相关,CD4＋百分百与FEV1/FVC、DLCO呈正相关,CD8＋百分百与FVC呈负相关,CD4＋/CD8＋与FVC、DLCO呈正相关.外周血TGF-β1水平与CD8＋呈正相关,与CD4＋/CD8＋呈负相关,TNF-α与CD4＋/CD8＋呈正相关,sIL-2R与CD4＋、CD4＋/CD8＋呈负相关,与CD8＋呈正相关.结论 不同分期尘肺患者均可能存在细胞免疫抑制状态,外周血TGF-β1高表达可能参与了尘肺的纤维化过程和肺功能的损害,TNF-α与尘肺分期有关可能与肺功能损害无关,sIL-2R高表达及CD4＋/CD8＋倒置形成的免疫抑制参与尘肺分期进展和肺功能损害.

Objective To investigate the peripheral blood and bronchoalveolar lavage fluid （BALF）, TGF-β1, TNF-α, sIL-2R level and peripheral blood T cell subsets and pneumoconiosis stage and lung function. Methods 68 cases of pneumoconiosis from April 2010 to July 2012 in General Hospital of Zhengzhou Coal Industry Group Co., Ltd. were chosen as pneumoconiosis group, the dust-exposed group and control group were selected with 35 cases in each group; the use of enzyme-linked immunosorbent assay in three sets of peripheral blood and pneumoconiosis in BALF TGF- β1, TNF-α, sIL-2R level, the loss of cells were detected by three sets of peripheral blood T cell subsets and detection of pneumoconiosis group lung function was analyzed. Results The difference of pneumoconiosis, dust-exposed group and control group serum TGF-β1 and sIL-2R level were statistically significant （P 〈 0.05）, the difference of serum TGF-β1, TNF-α, slL-2R level at different stages of pneumoconiosis group were statistically significant （P 〈 0.05）, the pneumoconiosis installments serum TGF-β1 SIL-2R water were significantly higher than those of dust-exposed group and the control group （P 〈 0.05）, II, III of serum TNF-α level were significantly lower than those of dust group and the control group （P 〈 0.05）; serum TGF-β1, sIL-2R level and pneumoconiosis stage were positively correlated （P 〈 0.05）, serum TNF-cdevel was negatively correlated （P 〈 0.05）. The differences of different stages of pneumoconiosis in BALF TGF-β1, TNF-α, sIL-2R level were statistically significant （P 〈 0.05）, patients with pnemnoconiosis in BALF TGF-β1, TNF-α level and staging were no significant correlation （P 〉 0.05）, slL-2R levels and staging of patients with pneumoconiosis in BALF were positively correlated （P 〈 0.05）. The difference of peripheral blood CD8 ＋ and CD4＋/CD8＋ of pneumoconiosis group, the dust-exposed group and the control group were statistically significant （P 〈 0.05）; the differences of pneumoconiosis installments peripheral blood CD4＋, CD8＋ and CD4＋/CD8＋ were statistically significant （P 〈 0.05）, stage 11, IU pneumoconiosis peripheral blood CD4＋ and CD4＋/CD8＋ were significantly lower than those of the dust-exposed group and the control group （P 〈 0.05）, I Phase m pneumoconiosis peripheral blood CD8＋ hundred percent were significantly higher than those of the dust-exposed group and the control group （P 〈 0.05）; peripheral blood CD4＋, CD8＋ hundred percent and pneumoconiosis stage were not significant correlation （P 〉 0.05）, and CD4＋/CD8＋ and pneumoconiosis stage were negatively correlated （P 〈 0.05）. Peripheral blood TGF-β1 level and FVC, FEVI/FVC and DLCO were negatively correlated with sIL-2R and FVC, DLCO were negatively correlated with TNF-α level and lung function were no significant correlation of CD4＋ hundred percent and FEV1/FVC, DLCO were positively correlated with CD8＋hundred percent and FVC were negatively correlated with CD4＋/CD8＋ and FVC, DLCO was positively correlated. Peripheral blood of TGF-β1 level of CD8＋ were related, and CD4＋/CD8＋ were negative related TNF-α and CD4＋/CD8＋ were positive related sIL-2R and CD4＋, CD4＋/CD8＋ were negatively correlated, and CD8＋ were being related. Conclusion The different stages of pneumoconiosis may exist in cellular immune suppression status, peripheral blood TGF-β1 high expression may participate in the pneumoconiosis fibrosis and lung function damage, TNF-α and pneumoconiosis stage may have nothing to do with the impairment of lung function, slL-2R ex- pression and CD47CD8＋ inverted inhibit the cellular immune function in pneumoconiosis stage progress and impair- ment of lung function.