我国主产地温石棉可吸入纤维致鼠肺损伤与抑癌基因p53、p16的表达

Lung injury and down regulation gene of p53 and p16 in rats induced by inhalable fibers from chrysotile asbestos in major mining areas of China

选取我国四大矿区主产地的温石棉,制备成粒径小于10μm的可吸入纤维,采用非暴露式气管滴注法染毒Wistar雄性大鼠,分别于1、3及6个月时称重并处死,迅速分离肺组织,观察肺形态并称量,计算肺脏器系数,并采用HE染色法利用光学显微镜观察肺组织病理改变,RT-PCR法测定p53、p16基因表达,探讨我国温石棉可吸入纤维的生物安全性。结果表明,四大主矿区的温石棉纤维粒度基本小于10μm,符合可吸入纤维粉尘标准,研磨前后纤维粉尘的结构和活性基团无破坏;染毒组Wistar大鼠体重明显减轻,肺重量显著增加,肺脏器系数变大;染毒组Wistar大鼠肺组织发生严重病理改变,出现不同程度的充血、水肿、炎性细胞浸润和纤维增生;染毒组Wistar大鼠肺p53、p16基因表达均降低。综合以上结果,发现我国四大主矿区温石棉的可吸入纤维粉尘均对Wistar大鼠肺组织呈不同程度和方式损伤。随着染毒时间延长,Wistar大鼠肺组织的抑癌基因p53、p16表达显著降低,推测我国四大矿区温石棉的可吸入纤维粉尘具有致肺癌的风险。

Chrysotile asbestos from four major mining areas in China was selected to prepare inhalable dust with particle size less than 10μm.Male Wistar rats were exposed by non-exposure tracheal instillation and weighed and sacrificed at the time in 1,3 and 6 months.The lung tissues were quickly separated,the lung morphology was observed and weighed,and the lung organ coefficient was calculated.The pathological changes of lung tissue were observed by light microscopy with HE staining,and the expression of p53 and p16 genes were determined by RT-PCR to investigate the biosafety of chrysotile fiber in China.The results show that the size of chrysotile fiber in the main mining areas was less than 10μm,which could meet the standards of inhalable dust.The structure and active groups of the dust before and after grinding were not damaged.The body weight of the Wistar rats was significantly reduced,the lung weight was significantly increased,and the lung organ coefficient was increased.The lung tissues of Wistar rats in the exposed group showed severe pathological changes,and there were different degrees of congestion,edema,inflammatory cell infiltration and fibrosis.The expression of p53 and p16 genes in the lungs of Wistar rats exposed to 1~6 months was significantly decreased.Based on the above results,it was found that the inhalable fiber dust of chrysotile asbestos in four major mining areas in China damaged the lung tissue of Wistar rats in different degrees and ways.With the prolonged exposure time,the expression of p53 and p16 in the lung of Wistar rats was significantly decreased.It is inferred that the inhalable fiber dust of chrysotile asbestos in four major mining areas in China has the risk of lung cancer.