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目的 研究三氧化二砷 (As2 O3)抗肝癌作用及其对肾脏的毒副作用并探讨其作用机制。方法 二乙基亚硝胺灌胃制备大鼠肝癌模型。以As2 O3或顺铂注射于大鼠腹腔 ,第 7、1 4、2 8天获取肝癌结节 ,光、电镜下观察肝癌细胞形态学变化 ,流式细胞仪检测凋亡及细胞动力学变化。第 2 8天获取肾脏 ,光镜下观察肾脏组织形态学变化 ,免疫组织化学SP法检测bcl 2、增殖细胞核抗原(PCNA)表达变化。结果 As2 O3诱导大鼠肝癌细胞凋亡 ,出现典型形态学改变 ;引起肝癌细胞凋亡率上升 ,中剂量组 (1mg/kg体重 )显著上升 ,明显高于顺铂组 (P =0 .0 0 0 )。顺铂组大鼠肾脏(4/ 7)镜下出现肾小管上皮细胞浊肿、变性 ,集合管内蛋白管型出现 ,而砷剂组无明显改变 (P =0 .0 1 3) ;砷剂组肾小管上皮细胞bcl 2表达增加 (P =0 .0 0 5) ,PCNA标记指数无明显改变 ,顺铂组PCNALI明显升高 (P =0 .0 0 1 )。结论 As2 O3可诱导大鼠肝癌细胞凋亡 ,且优于顺铂 ;与顺铂相比 ,无明显肾毒性
Objective To study the effect of arsenic trioxide (As 2 O 3) on hepatocarcinoma and its toxic effects on kidney and its mechanism of action. Methods Diethylnitrosamine was used to prepare rat hepatocarcinoma model. The ascites were injected into the peritoneal cavity of rats as As2O3 or cisplatin. The hepatic carcinoma nodules were obtained on the 7th, the 14th, the 28th and the 8th day respectively. Morphological changes were observed under light and electron microscopy. The apoptosis and cell motility were detected by flow cytometry. The kidneys were harvested on the 28th day, the morphological changes of the kidney were observed under the light microscope, and the expressions of bcl 2 and PCNA were detected by immunohistochemical SP method. Results As2 O3 induced apoptosis of hepatocellular carcinoma cells in rats with typical morphological changes. The apoptotic rate of hepatocellular carcinoma cells was increased, while that of middle dose group (1 mg / kg body weight) increased significantly, significantly higher than that of cisplatin group (P = 0.0000) . In the cisplatin group, renal tubular epithelial cells were found to have turbidity, degeneration and tubular protein tube appearance in the kidney (4/7) in the cisplatin group, while there was no significant change in the arsenic group (P = 0.013) The expression of bcl-2 in tubular epithelial cells increased (P = 0.0005), and the PCNA labeling index did not change significantly. The PCNALI in cisplatin group was significantly increased (P = 0.010). Conclusion As2 O3 can induce hepatocellular carcinoma cell apoptosis, and is superior to cisplatin; compared with cisplatin, no obvious nephrotoxicity