目的 研究雷公藤红素对人肝内胆管上皮细胞（human biliary epithelial cells，HIBEC）的毒性作用及机制。方法 通过CCK-8实验及显微镜观察记录雷公藤红素对细胞形态和活力的影响；通过细胞划痕实验检测雷公藤红素对细胞迁移能力的影响；通过流式细胞术检测雷公藤红素对细胞周期的影响和对细胞凋亡的诱导作用；通过qRT-PCR和Western blotting检测雷公藤红素对凋亡相关基因Caspase-3、Bax、Bcl-2基因和蛋白的表达情况。结果 雷公藤红素在400～2 000 nmol/L下，抑制细胞增殖，改变细胞形态；在200～800 nmol/L下，抑制细胞的迁移能力；在800～1 200 nmol/L下，出现G₀/G₁期阻滞作用；在400～1 200 nmol/L下，诱导细胞凋亡并增加相关基因的表达量。结论 雷公藤红素可通过影响胆管细胞活力，改变其迁移能力，阻滞细胞周期并促进细胞凋亡的方式产生胆管毒性。

Objective To investigate the toxicity and mechanisms of celastrol (CEL) on human biliary epithelial cells. Methods The effects of CEL on cell morphology and cell viability changes were observed by CCK-8 experiment and microscope. Cell scratch experiment was used to detect the effect of CEL on cell migration. The effects of CEL on cell cycle and cell apoptosis were detected by flow cytometry. The mRNA and protein expression of apoptosis-related genes Caspase-3, Bax and Bcl-2 were detected by qRT-PCR and Western blotting. Results CEL inhibited cell proliferation and changed cell morphology at 400—2 000 nmol/L. At 200—800 nmol/L, cell migration was inhibited. At 800—1 200 nmol/L, G₀/G₁ phase was arrested. At 400—1 200 nmol/L, cell apoptosis was induced and the expression of apoptosis-related genes was increased. Conclusion CEL showed cholangiocyte toxicity through affecting cell viability, cell migration, preventing cell cycle and promoting cell apoptosis of human biliary epithelial cells.

北京市科技新星课题（Z191100001119088）；北京市双一流课题（1000041510087）