21-氨基类固醇抗石英细胞毒性及抑制其促成纤维细胞生长的研究  

Protective effects of Lazaroids(U-75412E) against quartz-induced cytotoxicity and proliferation of fibroblast

作　　者：黄曙海[1] 樊建康[1] 王力珩[1] Val Vallyathan 

机构地区：[1]广西壮族自治区职业病防治研究所中毒毒理研究室,南宁530021 [2]美国职业安全与卫生研究所

出　　处：《中华劳动卫生职业病杂志》2000年第1期42-44,共3页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：广西壮族自治区科技厅留学回国人员基金!资助项目 (桂科回97350 0 9)

摘　　要：目的　研究 2 1 氨基类固醇 (Lazaroid ,U 75 412E)在体外对石英毒性的抑制作用。方法　观察体外培养的肺泡巨噬细胞 (AM)释放H2 O2 、乳酸脱氢酶 (LDH)、超氧化物歧化酶 (SOD)和β N 乙酰氨基葡萄糖苷酶 (NAG)的水平 ,评价U 75 412E对石英细胞毒性的消除能力 ;电子自旋共振俘获法评价U 75 412E清除石英催化H2 O2 产生·OH的作用 ;噻唑蓝比色法比较U 75 412E对矽肺大鼠肺泡AM促成纤维细胞 (FB)生长活性的抑制作用。结果　在U 75 412E作用下 ,与石英共孵的肺泡AM释放H2 O2 、SOD、LDH的水平显著下降 ,40 μmol/LU 75 412E组各值分别为 (0 .16± 0 .0 4)nmol/L、(48.6± 2 2 .2 ) μg/L、(33.0± 4.6 )U/L ,而阳性对照组分别为 (0 .6 3± 0 .0 7)nmol/L、(117.5± 30 .3) μg/L、(6 0 .3± 5 .5 )U/L。在Fenton反应体系中 ,石英催化H2 O2 生成·OH ,平均峰值为 (5 3.2 5± 2 .3)mm ;当与U 75 412E共存时 ,反应体系中的·OH水平显著下降 ,平均峰值为 (2 8.4±1.3)mm。矽肺或受石英攻击的肺泡AM培养液促进了NIH 3T3细胞增殖 (平均指数 :77.8± 8.0、85 .9± 7.0 ) ,U 75 412E显著抑制了这一活性 (平均指数 :5 8.0± 15 .4、5 2 .6± 11.8)。结论　U 75 412E具有较强的清除·OH、保护AM抵御石英细胞毒性、抑?Objective To investigate the protective effects of Lazaroids(U 75412E) against crystalline silica induced cytotoxicity and macrophage mediated proliferation of fibroblast.Methods As indicators of quartz induced cytotoxicity and protection by U 75412E, the levels of H 2O 2, SOD, LDH and NAG released in vitro from rat alveolar macrophages were measured after treated with and without quartz or U 75412E. Hydroxyl radical (·OH) generated by Fenton reaction was evaluated using ESR spin trapping competition reactions. Inhibition of Lazaroids on proliferative activity of silicotic pulmonary macrophages was tested using MTT colorimetry.Results Quartz stimulated macrophages cocultured with Lazaroids at 40 μmol/L in vitro released significantly lower levels of H 2O 2,SOD and LDH (0.16±0.04) nmol/L, (48.6± 22.2) μg/L,(33.0±4.6) U/L,respectively vs (0.63±0.07) nmol/L,(117.5±30.3) μg/L, (60.3±5.5) U/L.Lazaroid strongly scavenged ·OH generated by quartz mediated reaction from H 2O 2 [(28.4±1.3) mm, vs (53.25±2.3) mm].Pulmonary macrophages derived from silicotic rats or stimulated by quartz in vitro again showed significantly potent activity to stimulate fibroblast NIH 3T3 to proliferate(proliferation index:77.8±8.0 and 85.9±7.0 vs 58.0±15.4 and 52.6±11.8). Conclusion Lazaroid U 75412E could reduce crystalline silica induced cytotoxicity,scavenge hydroxyl radicals and inhibit the activity of alveolar macrophages to promote fibroblast proliferation.

关 键 词：氨基类固醇 石英 毒性抑制 成纤维细胞 矽肺 

分 类 号：R114[医药卫生—卫生毒理学]