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| 阿司匹林中断硫代乙酰胺诱发大鼠胆管上皮癌变 |
| 王革芳1,陈颖2,魏培莲3,赵行3,李超富3,高云姝3,于观贞3* |
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(1. 解放军 85 医院肿瘤科, 上海 200052;
2. 海军军医大学(第二军医大学)长海医院病理科, 上海 200433;
3. 上海中医药大学附属龙华医院肿瘤科, 上海 200032
*通信作者) |
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| 摘要: |
| 目的 构建胆管癌原位诱导大鼠模型，应用阿司匹林干预该模型，观察阿司匹林对胆管癌的影响。方法 给予SD雄性大鼠饮用含有硫代乙酰胺（300 mg/L）的饮用水，第8、12、16和20周时H-E染色分别观察肝脏成瘤情况，采用免疫组化法检测碳酸酐酶2（CA-2）在肝脏组织中的表达。另选取SD雄性大鼠，在硫代乙酰胺饲养12周后开始用阿司匹林处理，第3、6个月取出肝脏，H-E染色观察肝脏成瘤情况，免疫组化法检测CA-2的表达变化。取胆管癌细胞QBC939，予以阿司匹林（0 mmol/L和5 mmol/L）处理，培养48 h后采用蛋白质印迹法检测细胞中CA-2的表达。结果 硫代乙酰胺饲养第12周时部分大鼠肝内可见明显的纤维化；第16周时所有大鼠肝内均出现大量纤维组织增生，镜下可见肿瘤或疑似肿瘤；第20周时所有大鼠肝脏均形成肉眼和镜下可见的肿瘤。阿司匹林处理6个月后，大鼠肝内肿瘤或疑似肿瘤的发生率为28.6%（2/7），而未处理组中大鼠肝内肿瘤或疑似肿瘤的发生率为100%（7/7）。大鼠肝脏组织中CA-2的表达水平随胆管癌病情的进展逐渐升高，而阿司匹林处理后大鼠肝脏组织中CA-2的表达减弱。5 mmol/L阿司匹林处理48 h后QBC939细胞中CA-2的表达与未处理对照组相比下调（P<0.01）。结论 硫代乙酰胺能成功诱导肝内胆管癌的发生，阿司匹林能阻断该过程，可用于预防肝内胆管癌。 |
| 关键词: 胆管癌 阿司匹林 硫代乙酰胺 碳酸酐酶2 |
| DOI：10.16781/j.0258-879x.2018.03.0285 |
| 投稿时间：2017-11-01修订日期：2017-12-29 |
| 基金项目:国家自然科学基金（30901794，81572856），上海市浦江人才计划项目（13PJD002），全军医药卫生科研基金（14ZD16），上海中医药大学附属龙华医院高层次人才引进项目（LH02.51.002）. |
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| Aspirin interrupts bile duct carcinoma in rats induced by thioacetamide |
| WANG Ge-fang1,CHEN Ying2,WEI Pei-lian3,ZHAO Xing3,LI Chao-fu3,GAO Yun-shu3,YU Guan-zhen3* |
(1. Department of Oncology, No. 85 Hospital of PLA, Shanghai 200052, China;
2. Department of Pathology, Changhai Hospital, Navy Medical University(Second Military Medical University), Shanghai 200433, China;
3. Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
*Corresponding author) |
| Abstract: |
| Objective To establish a thioacetamide (TAA)-induced bile duct carcinoma rat model and to observe the effect of aspirin on bile duct carcinoma by interrupting the model. Methods Sprague-Dawley (SD) male rats were given drinking water containing TAA (300 mg/L) for 5 months, and tumor formations of the livers were observed by H-E staining at the 8th, 12th, 16th, and 20th weeks, respectively. The expression of carbonic anhydrase 2 (CA-2) in liver tissues was also detected by immunohistochemistry. SD male rats were also selected and treated with aspirin after exposing to TAA for 12 weeks. And then the tumor formations of the livers were observed by H-E staining at the 3rd and 6th months, and the expression of CA-2 was detected by immunohistochemistry. Bile duct carcinoma cells QBC939 were obtained and treated with aspirin (0 mmol/L and 5 mmol/L), and the expression of CA-2 was detected by Western blotting after culturing for 48 h. Results Obvious fibrosis was found in the livers of some rats at 12th weeks after exposing to TAA; large number of fibrous tissue hyperplasia and microscopic or suspected tumors were found in the livers at the 16th weeks; visible tumors in the livers were found in all the rats at the 20th weeks. The incidence of hepatic tumors or suspected tumors was 28.6% (2/7) in rats treated with aspirin for 6 months, while it was 100% (7/7) in rats without aspirin treatment. The expression of CA-2 in liver tissues was gradually increased with the development of bile duct carcinoma in rats, while the expression of CA-2 in liver tissues was decreased after treating with aspirin. The expression of CA-2 in QBC939 cells treated with 5 mmol/L aspirin for 48 h was significantly decreased versus the untreated control group (P<0.01). Conclusion TAA can successfully induce intrahepatic bile duct carcinoma. Aspirin can interrupt the development of bile duct carcinoma and may be used to prevent intrahepatic bile duct carcinoma. |
| Key words: carcinoma of bile duct aspirin thioacetamide carbonic anhydrase 2 |
