关键词: 除草醚, II型肺上皮细胞, 增殖, 凋亡

Abstract: BACKGROUND ＆ AIM: Nitrofen is a herbicide used to establish the pulmonary hypoplasia model. The current study was performed to explore the effects and mechanisms of nitrofen on proliferation and apoptosis of cultured type II pneumocytes. MATERIALS AND METHODS: Type II pneumocytes A549 were treated with 20,40 and 80 μmol/L of nitrofen. Cellular proliferation was measured by MTT colorimetry, colony formation assay. Western blot and real_time RT_PCR were performed to detect the PCNA expression. Apoptosis was assayed by TUNEL labeling and acridine orange_ethidium bromide staining. Expression of apoptosis_related genes was detected by western blot. RESULTS: Compared with controls, administration of 20,40 and 80 μmol/L nitrofen for 12－48 hrs resulted in 12.43％－71.73％ decrease in proliferation (P<0.01), and 79.2％ decrease in colony formation (P<0.01) of A549 cells. The PCNA protein and mRNA within nitrofen_treated cells were reduced in a time_and dose_dependent manner(P<0.01). Partial nitrofen_treated A549 cells presented morphological changes of apoptosis, with apoptotic rates of 8.0％－22.5％ (P<0.01), which could not be abolished by the pan caspase inhibitor zVAD_fmk. The expression of anti_apoptotic Bcl_xL was significantly down_regulated (P<0.01). CONCLUSION: Nitrofen decreased proliferation of cultured type II pneumocytes associated with down_regulation of PCNA, and induced apoptosis associated with suppressed Bcl_xL expression.

Key words: nitrofen, type II pneumocytes, proliferation, apoptosis