促进瘤周纤维化治疗中晚期肝癌的实验研究  

Acceleration of fibrosis around tumor in treatment of hepatic carcinoma

作　　者：曹罡[1] 解立怡[1] 刘清峰[1] 李宗芳[1] 徐心[1] 刘效恭[1] 

机构地区：[1]西安交通大学第二医院普外科,西安市710004

出　　处：《中华肝胆外科杂志》2004年第3期173-176,共4页Chinese Journal of Hepatobiliary Surgery

摘　　要：目的　为解决中晚期肝癌临床切除率低、手术创伤大、转移率高等问题 ,我们设计了含瘤肝叶胆管支、门静脉支联合结扎的方法 ,对大鼠移植性肝癌模型进行了治疗性研究。方法　应用R 35大鼠肝癌瘤株制备Wister大鼠移植性肝癌模型 ,分组实施含瘤肝叶的门静脉支胆管支联合结扎术及对照手术。对比观察大鼠死亡率、转移率、治疗成功率 ;原位末端检测观察癌细胞凋亡情况 ;免疫组化测定肝癌细胞MMP 9表达情况 ;免疫组化方法观察Ito细胞、Ⅰ、Ⅳ型胶原的增生情况 ;原位杂交检测α1Ⅰ、α1Ⅳ型前胶原mRNA表达及定位情况。结果　手术组与对照组相比死亡率 31 3%∶6 8 8%、腹腔转移率 31 3%∶6 2 5 %、肝内转移率 12 5 %∶4 3 8%、腹腔转移合并肝内转移率 6 3%∶37 5 %、治疗成功率为 4 3 8% ;对照组平均AI值 =4 32± 0 2 4 ,治疗组平均AI值 =12 80± 1 17;纤维包裹癌团MMP 9表达总阳性率为 2 4 2 4 %、强阳性率为 9 0 9% ,自由生长癌团MMP 9表达总阳性率为 87 88%、强阳性率为 4 2 4 2 % ;Ito细胞和Ⅳ型胶原完成早期瘤周纤维包裹 ,为I型胶原的沉积做出引导和铺垫 ;癌周纤维化早期 ,Ito细胞及MF主要对α1(Ⅳ )前胶原mRNA做出表达 ,中期α1(Ⅰ )前胶原mRNA杂交信号开始出现并增多 ,后期二者趋于稳定。结论　联?Objective To solve the problem of unsuccessful treatment of the hepatic carcinoma. Methods R-35 cells were cultured and then implanted into rats' liver to establish the hepatic cancer model. The combined ligation of the very lobe's portal vein and bile duct was performed in the experimental group while only the simple control surgery was done in the control group. The death rate of rats, successful rate, metastatic rate of tumor and development of fibrosis around the tumor were determined. The expression of MMP-9, generation of Ito cells and the type Ⅰ and Ⅳ collagen were determined with immunohistochemistry. Meanwhile, the cell apoptosis was observed with TUNEL. The expression of procollagen α 1 (Ⅰ) mRNA and α 1(Ⅳ) mRNA was analyzed by in situ hybridization. Results The tumor in the liver lobe is successfully surrounded by dense fibers in 16 weeks after the operation. The experimental group had a low death rate and metastatic rate and the curative rate was 43.8%. The expression of MMP-9 was obviously decreased in the cancer cells tightly surrounded by fibers. Cell apoptosis was more obvious in the cancer cell groups inside the surrounding fibers. The Ito cells and type Ⅳ collagen accomplished the early fibrotic surrounding, which became the basic structure for type Ⅰ collagen's generation. The expression of procollagen α 1 (Ⅰ) mRNA and α 1(Ⅳ) mRNA was mainly found in the Ito cells and MF. Meanwhile, it could be seen inside the fibers. Conclusions The combined ligation makes the fibrosis develop to tightly surround the tumor. As a result, the growth and metastasis of the tumor is limited. The dense fibers around the tumor also increase the apoptotic rate of tumor cells and decrease the expression of MMP-9 in the cells to limit their growth and metastasis. The key cells for expression of procollagen α 1 (Ⅰ) mRNA and α 1(Ⅳ) mRNA are Ito cells. Their number and activity affect not only the course of liver fibrosis but also treatment of the tumor.

关 键 词：瘤周纤维化治疗 肝癌 实验研究 癌细胞凋亡 原位杂交 

分 类 号：R735.7[医药卫生—肿瘤]