c-fos基因在长期砷暴露大鼠肾小管上皮细胞的表达

Expression of c-fos Gene in Renal Epithelial Cells of Rats Chronically Exposed to Arsenic

目的研究凋亡调控基因c-fos对亚慢性砷中毒大鼠肾小管上皮细胞凋亡的影响,探讨凋亡机制在砷中毒肾小管细胞损伤中的意义。方法 SD大鼠随机分为高、低砷剂量组和对照组,砷染毒组自由饮用含砷水[高砷组:50mg/L,相当于10mg/(kg·d);低砷组:2mg/L,相当于0.4mg/(kg·d)],对照组饮蒸馏水。连续染砷16周后,以光镜观察肾小管上皮细胞形态结构变化并以免疫组化SABC方法检测肾小管上皮细胞c-fos的表达,并进行图像分析、计数。结果各砷染毒组肾小管上皮细胞c-fos阳性细胞数与对照组比较均增多,灰度值均降低,高剂量组肾小管上皮细胞c-fos阳性细胞数与低剂量组比较均增多,灰度值均降低,差异均有统计学意义(P<0.01)。光镜下砷染毒组肾小管细胞可见空泡样变,核固缩,刷状缘不整齐,管腔狭小等形态学损伤改变。结论砷能致大鼠肾小管上皮细胞组织病理损害,c-fos基因的高表达可能参与了砷中毒肾小管上皮细胞凋亡的调控。

Objective To investigate the influence of c-fos gene on the apoptosis of renal tubular epithelial cells of rats chronically exposed to arsenic. Methods Sprague-Dawley （SD） rats of cleanliness grade were randomly divided into three groups （low-, high-dose arsenic group and control group）, the arsenic exposed groups were administered with drinking water containing As203 [high-dose： 10 mg/（kg·d）,low-dose： 0.4 mg/（kg·d）],control group with distilled water, for 16 consecutive weeks. The morphological changes of renal epithelial cells of rats were observed under light microscope, the expression ofc-fos was detected by SABC immunohistoehemistry and image analysis was done. Results Compared with the control group, more renal epithelial cells with the expression of c-los and lower OD value were found in both of high-dose and low-dose groups. Compared with low-dose group , more renal epithelial cells with the expression of c-fos and the lower OD were found in high-dose group.The renal tubular epithelial cells in arsenic exposed groups revealed pathological injury including vacuolar degeneration, karyopyenosis, irregular brush border, luminal stenosis. Conclusion Chronic arsenic exposure can cause evidently pathological changes in renal tubular epithelial cells.The up-regulated expression of c-fos gene may play a regulatory role in the apoptosis of the renal tubular epithelial cells induced by chronic arsenic exposure.