二乙基亚硝胺诱发大鼠肝癌过程中肝脏胶原的动态观察  

Sequential study of liver collagen fibers in diethylnitrosamine-induced hepatocarcinogenesis in rats

作　　者：周陈杰[1] 宫绪萌[1] 蔡理[1] 汪艳[1] 高毅[1] 

机构地区：[1]南方医科大学珠江医院肝胆二科,广州510282

出　　处：《第二军医大学学报》2014年第6期626-630,共5页Academic Journal of Second Military Medical University

摘　　要：目的动态观察大鼠肝脏癌变过程中胶原纤维的变化特点，为肝癌发病机制的研究提供参考。方法将50只雄性Wistar大鼠（体质量100～120g）随机分为模型组和对照组，分别腹腔注射二乙基亚硝胺（DEN）50mg／kg（加生理盐水至0．1mL）或生理盐水（0．1mL），均每周2次，连续4周后改为每周1次，至14周停止。处死大鼠，取肝脏病变组织及周边正常组织，通过H-E染色、Masson染色、网状纤维染色观察其形态学改变；采用荧光定量PCR技术检测大鼠肝组织Ⅰ型及Ⅲ型胶原mRNA的动态表达；采用明胶酶谱法检测大鼠肝组织中基质金属蛋白酶（MMP）含量变化。结果DEN诱癌开始5周后大鼠肝组织肝硬化形成，14周后诱导出肝癌。相应地，肝组织内胶原沉积持续增加，癌灶内胶原含量则明显少于癌周组织，并呈进行性减少；MMP-2、MMP-9在癌周组织和癌组织中的变化趋势则与胶原含量变化相反。结论DEN诱导的大鼠肝脏癌变过程中，胶原纤维在肝组织中沉积增加，在肝癌组织中则减少，随着肝癌的进展，癌组织内胶原进一步减少，提示肝硬化组织癌变过程中胶原纤维可能被降解。Objective To observe the sequential changes of collagen fibers in rats with diethylnitrosamine （DEN）-induced hepatocellular carcinoma （HCC）, so as to provide a reference for pathogenesis research of HCC. Methods Fifty male Wistar rats, weighing 100-120 g, were randomly divided into normal group and HCC model group. The model group was intraperitoneally administered with 50 mg/kg DEN （0. 1 mL）, twice a week for 4 weeks, then once a week for another 10 weeks. The control group was given normal saline （0.1 mL） in the same manner. Finally the rats were sacrificed; the normal and diseased liver tissues were observed by H-E, Masson and argyrophiIic fiber staining. The expression of collagen type ~[ and type I]] mRNA was detected by fluorogenic quantitative PCR; the expression of matrix metalloproteinase （MMP） was examined by gelatinases spectrometry. Results Cirrhosis was found in rats 5 weeks after treatment with DEN and HCC was induced 14 weeks after DEN treatment; collagen deposition in liver tissues increased in a progressive manner, and the collagen contents in the HCC tissues was greatly less than that in the adjacent tissues, showing a decreasing trend. The contents of MMP-2 and MMP-9 in the HCC and adjacent tissues had opposite changes compared with collagen. Conclusion Collagen deposition in cirrhosis liver tissue is increased during the process of DEN-induced HCC, but it is decreased in HCC tissues in a progressive manner, which indicates that collagen might be degraded during the progression from cirrhosis to HCC.

关 键 词：肝肿瘤 肝硬化 二乙基亚硝胺 胶原纤维 

分 类 号：R735.7[医药卫生—肿瘤]