铀矿尘致大鼠肺纤维化过程中Ⅰ和Ⅲ型胶原及层粘连蛋白表达的变化

The characteristics of type Ⅰ - Ⅲ collagen and LN in pulmonary fibrosis induced by uranium ore dust in rats

目的探讨铀矿尘致大鼠纤维化过程中Ⅰ、Ⅲ型胶原、层粘连蛋白（Laminin，LN）表达的变化特征。方法60只Wistar大鼠随机分为铀矿尘组（30只）和对照组（30只），铀矿尘组大鼠一次性非暴露气管内滴注20mg／ml的粉尘悬液1ml，对照组大鼠一次性气管内滴注生理盐水1ml，分别于处理后7、14、21、30及60d每组随机处死6只，取肺组织，HE染色观察肺组织形态学改变，天狼猩红染色法观察肺组织I、Ⅲ型胶原变化，免疫组织化学法检测LN蛋白的表达。结果铀矿尘致肺组织纤维化过程中可见Ⅰ、Ⅲ型胶原的大量增生，染尘后早期主要以Ⅰ型胶原增生为主。铀矿尘组21、30、60d时Ⅰ型、Ⅲ型胶原纤维面积百分比明显增高，与对照组比较，差异均有统计学意义（P〈0．05或P〈0．01）。LN主要见于肺组织内血管、支气管周围、血窦壁以及肺间隔的基底膜，形态上以增粗的线状或丛状分布为主。铀矿尘组21、30、60d时肺组织中LN阳性细胞积分吸光度（14．89±2．25、22．98±2．29、30．34±2．19）增加，与对照组（9．06±1．21、8．98±0．86、10．04±2．00）比较，差异有统计学意义（P〈0．05，P〈0．01）。结论铀矿尘诱导大鼠肺组织纤维化早期以Ⅰ型胶原纤维为主，后期Ⅰ型、Ⅲ型胶原纤维均大量增多，分布范围扩大。肺组织过程中有LN高表达。

Objective To explore the characteristics of LN and type Ⅰ , Ⅲ collagen in pulmonary fibrosis induced by uranium ore dust in rats. Methods 60 aduh Wistar rats were divided randomly into two groups, control group （30 rats）and uranium ore dust group （30 rats）. Non-exposed intratraeheal instillation method was used. Uranium ore dust group was exposed 20 mg/ml uranium ore dust suspension lml per rat, meanwhile control group was exposed normal saline lml per rat. Post-exposed the 7, 14, 21, 30 and 60 d, 6 rats in each group were killed randomly, lung tissue were collected. The pathological changes in lung tissue were observed by microscope using HE staining, the collagen Ⅰ and Ⅲ in lungs were observed by polarizing microscope using Biebrieh scarlet staining. The expression of LN protein in lung tissue was observed by immunohis- tochemistry-SP. Results During lung fibrosis, a large amount of the proliferated Ⅰ and Ⅲ collagen in lungs were observed. Post-exposure to uranium ore dust, the characteristics in proliferated collagen in lungs were type Ⅰ collagen deposited in lung interstitium mainly in the early stage. The area percentage of collagen Ⅰ and Ⅲ was increased significantly at 7,14, 21, 30 and 60 d in the experimental group as compared with that in the control group （P〈0.05 or P〈0.01 ）. The over expression of LN in the lung tissue were observed. The expression of LN was distributed in the lung tissue as thickening of the linear or cluster. The integral optical density of LN was increased significantly at 21,30 and 60d in the experimental group as compared with that in the control group （P〈0.05 or P〈0.01 ）. Conclusions After exposure to uranium ore dust, the characteristics in proliferated collagen in lungs are the type of Ⅰ collagen deposited in lung interstitium mainly in the early stage, while the type of Ⅲ collagen increase significantly at the later period. The overexpression of LN exists in the process of pulmonary fibrosis. It suggests that LN has a role effect in the process of pulmonary fibrosis.