大鼠硬金属肺病模型建立及KL-6与TGF-β表达的研究

Study on the establishment of HMLD model and the expression of KL-6/TGF-beta in rat

目的 建立大鼠硬金属肺病（HMLD）动物模型,筛选HMLD的诊断指征,探讨硬金属肺病的发病机制.方法 SPF级SD大鼠随机分为5组,每组8只,分别为生理盐水组、纯钴组、纯碳化钨组、二氧化硅组和硬质合金（HM）组.各组大鼠用肺部气管雾化滴注给药套装分别给予10 mg/只生理盐水、纯钴、纯碳化钨、二氧化硅和硬质合金混悬液.8周后进行肺部CT扫描及肺组织进行病理学观察,同时取血清及肺泡灌洗液（BALF）进行唾液酸化糖蛋白（KL）-6、转化生长因子（TGF）-β1以及TGF-β2的酶联免疫吸附测定（ELISA）.结果 染毒8周大鼠HM组肺组织结构破坏,间质出现大量多核巨细胞及类上皮细胞,且肺部CT扫描影像出现阴影异常.BALF中KL-6、TGF-β1、TGF-β2表达各组存在差异,差异均有统计学意义（P＜0.05）.血清中KL-6、TGF-β1表达各组存在差异,差异均有统计学意义（P＜0.05）;TGF-β2表达各组差异无统计学意义（P＞0.05）.结论 成功建立大鼠HMLD动物模型,大鼠活体肺部CT扫描可作为HMLD诊断的辅助手段;血清及BALF中KL-6、TGF-β2表达对大鼠HMLD疾病模型的特异性不高,而TGF-β1对大鼠HMLD的确定有辅助诊断参考价值.

Objective To establish an animal model of hard metal lung disease （HMLD） in rats,and to screen the indications for diagnosis of HMLD.Methods The rats were randomly divided into 5 groups,each group included 8 rats：saline group,pure cobalt group,pure tungsten carbide group,silica group and hard metal （HM）group.10 mg subjects were administered in each group by using the pulmonary endotracheal tube.After 8 week,the lung CT scan and lung tissue pathology were observed,the serum and bronchoalveolar lavage fluid （BALF） were collected for KL-6,TGF-beta1 and TGF-beta2.Results The lung tissue structure of HM group was destroyed,a large number of nuclear giant cells and epithelial like cells appeared in the stroma,and uncommon CT scan images appeared in the lung.KL-6,TGF-beta1,TGF-beta2 expression in each group was not the same,the difference was statistically significant （P〈0.05）.The expression of KL-6 and TGF-beta1 in serum was not identical in all the groups,the difference was statistically significant （P〈0.05）.The expression of TGF-beta2 had no significant difference between the groups （P〉0.05）.Conclusion Rats can be successfully established HMLD model,rats in vivo lung CT scan images appear abnormal,which are provided with assistant diagnostic value for HMLD.The expression of KL-6 and TGF-beta2 in serum and BALF on HMLD rats are not highly specific,and TGF-beta1 has reference value in the rat HMLD auxiliary diagnosis.