BHT亚急性毒性及致肺巨噬细胞凋亡作用
Apoptosis effect on pulmonary macrophage induced by butylhydroxytoluene under subacute toxic exposure in rats
-
摘要:目的 研究2, 6-二叔丁基对甲酚(BHT)对大鼠亚急性毒性及其对肺巨噬细胞凋亡作用。方法 SD大鼠40只, 随机分为BHT高、中、低剂量组(300, 600, 1 200 mg/kg)、吐温-80溶剂对照和蒸馏水对照组, 每天灌胃, 连续8 d。处死动物, 行肺灌流, 用荧光染色及彗星试验检测巨噬细胞凋亡; 测脏器系数、一般指标和病理检查。结果 染毒第4 d, 动物体重开始下降, 以高剂量组下降为显著, 第8 d, 动物体重有增加的趋势, 仍低于正常组, 高剂量染毒组大鼠体重依然明显低于中低剂量组。肺和肝脏器系数随染毒剂量增加而增高。病理检查, 中、高剂量组大鼠肺泡间隔增厚, 炎细胞浸润、无纤维化。肝脏中央静脉周围细胞有点状坏死, 以高剂量更明显, 并出现假小叶和肝纤维化。血生化显示肝功能异常, 且随剂量增加, 损伤加重。细胞凋亡检测显示, 中、高剂量的BHT具促进肺巨噬细胞凋亡的作用。结论 亚急性BHT大剂量染毒可造成大鼠肺、肝等脏器功能性和器质性损伤, BHT可诱发肺巨噬细胞凋亡的产生。Abstract:Objective To study the apoptosis effect induced by Butylhydro xytoluene(BHT)on macrophage in lungunder subacute toxic exposure.Methods 40 SD rats were divided randomly into three different doses g roups of BHT and one group as menstruum control and one group as control.The rats of BHT groups were given separately by the dose of 300, 600 and 1 200 mg/kg(po)for 8 days.Results At the end of exposure, the body weight(bw)of rat in BHT exposed groups were all decreased in the fourth day, especially the high dose group.At the eighth day the bw of rats in BHT groups have trends to increase, but which were still lower than control group.Coefficient of lung and liver were increased with the BHT dose raising.SGPT, SGOT in liver also raised and sho wn in a manner of dos-eeffect relationship, and inosine also be found raising in high BHT dose group.Pulmonary patho logy determination showed that there were raised alveolus spacing and interstitial inflammation in middle and high BHT dose groups, but fibrosis were not found.Hepatic pathology showed that some of point necrosis were found in cells which were around the liver central veins, especially the high dose g roup in which pseudolobules and fibrosis also be found.By means of technology of PI fluorescence stain and comet assay, ithad been found that BHT could induce apoptosis to pulmonary macrophage in the perfusate of isolated perfused rat lungs.Conclusion BHT may cause functional and organic damage of lung and liver, and it can induce apoptosis to pulmonary macrophage in rats.
下载: