中文摘要：

目的观察脱氧胆酸（DCA）对AR42J胰腺腺泡细胞的损伤作用并探讨其对核转录因子（TF）活性的影响。方法应用噻唑蓝（MTF）比色法检测DCA作用下细胞存活率改变，流式细胞术AV／PI双染法检测细胞的凋tk／坏死率。细胞经0．4mmoL／LDCA分别作用15min、30min、4h后收集培液上清，收集细胞并提取细胞质和细胞核蛋白，分别检测培液上清和胞质淀粉酶的活性，利用Luminex检测细胞核，11F的DNA结合活性。结果DCA对AR42J胰腺腺泡细胞的损伤作用呈浓度和时间依赖性，对细胞质内和培液中的淀粉酶水平无明显影响。在检测的40种TF活性变化中，DCA诱导ATP2、AR33、STATS、NFAT、FKHR和NKX-2．5这6种TF活性明显升高，而RUNX／AML、NF-Y、MEF2和E2F1这4种11F活性则明显下降，其余30种TF活性无明显变化。结论DCA对腺泡细胞的损伤作用主要表现为凋亡和坏死，对细胞内酶的合成和分泌功能没有明显影响。DCA诱导细胞核TF活性的变化，可能是其诱导细胞损伤的分子生物学基础。

英文摘要：

Objective To study the cytotoxic effect of desoxycholic acid （DCA） on pancreatic acinar cells AR42J, its impact on the synthesis and secretion function of amylase, and the influence on the activity of nuclear transcription factor （TF）. Methods The cytotoxic effect of DCS was detected in rat AR42J cells by using methyl thiazol tetrazolium （MTr） assay. The rate of apoptosis or necrosis was determined by flow cytometry. After the cells were incubated with DCA （0. g mmol/L） for 15 min, 30 min, or 4 h, the medium was collected to detect the activity of amylase. The cytoplamic protein was extracted to detect the activity of amylase, and nuclear protein was extracted to detect the DNA binding activity of 40 TFs by Luminex. Results DCA exerted cytotoxic effects on AR42J cells in a time- and dose-dependent man- ner, and induced cell apoptosis and necrosis. DCA had no significant influence on the amylase synthesis and secretion function of acinar cells. For the DNA binding activity of the 40 nuclear TFs, 0. 4 mmol/L DCA up-regulated the activity of ATF2, AR33, STATS, NFAT, FKHR, and NKX-2. 5, but down-regulated the activity of RUNX/AML, NF-Y, MEF2, and E2F1. Conclusion DCA can cause AR42J pancreatic acinar cell damage by apoptosis and necrosis in a dose- and time-dependent manner. The alteration of DNA binding activity of TFs induced by DCA may be the molecular mechanism of cell damage.