伊立替康耦合亚甲蓝靶向示踪大鼠胃癌淋巴结的研究  

Irinotecan coupled with methylene blue as targeted tracer for lymph nodes of gastric tumor in rats

作　　者：陈晓鹏[1] 童朝刚[3] 徐龙帅[1] 张帆[2] 王永[1] 王东[1] 王冠男[1] 

机构地区：[1]皖南医学院弋矶山医院普外科,安徽芜湖241001 [2]皖南医学院弋矶山医院病理科,安徽芜湖241001 [3]安徽省巢湖市第一人民医院普外科

出　　处：《中华实验外科杂志》2010年第4期435-437,共3页Chinese Journal of Experimental Surgery

基　　金：安徽省临床医学重点学科基金资助项目（05A016）

摘　　要：目的探讨伊立替康与亚甲蓝耦合液在大鼠胃癌淋巴结中的靶向示踪作用及其机制。方法应用Walker-256细胞株建立大鼠胃癌模型，免疫组织化学检测癌组织中伊立替康底物拓扑异构酶Ⅰ（topoⅠ）的表达。分别用5、10、20、40mg伊力替康粉剂耦合2ml亚甲蓝注射液，另用中华墨汁、纳米活性炭和亚甲蓝作为对照。70只胃癌大鼠分为7组，瘤周4点浆膜下微针分别注射上述7种染色剂。观察各组淋巴结染色、褪色时间、染色淋巴结数等指标。结果（1）建立大鼠胃癌模型符合实验要求，癌组织中topoI的表达显著增强。（2）中华墨汁、纳米活性炭和亚甲蓝到达胃癌第1站淋巴结平均时间依次为20、4min和14S；4组耦合剂分别为19、27、41、61s。染料运行至第2站淋巴结的平均时间与之相似。（3）中华墨汁、纳米活性炭和亚甲蓝组平均染色淋巴结数量分别为2、7和8枚；各耦合剂组淋巴结检出数量逐渐增加，依次为8、8、9和11枚。（4）淋巴结褪色时间中华墨汁〉24h，亚甲蓝102min，其余各组介于两者之间。（5）各组动物未见明显不良反应。结论通过靶向结合癌组织中的topoⅠ，适当剂量的伊立替康与亚甲蓝耦合剂可显著延长大鼠胃癌淋巴结染色和褪色时间，提高淋巴结靶向示踪效率。Objective To evaluate the targeted tracing of irinotecan coupled with methylene blue （MB） for lymph nodes of gastric cancer in rats and explore its mechanism. Methods The rat implanted gastric tumor model was established with malignant tumor cell line Walker-256 and identified, and the topoismerase Ⅰ（topo Ⅰ）, the substrate of irinotecan, was immunohistologically detected in cancer tissues. Five, 10, 20 and 40 mg of irinotecan powder was coupled with 2 ml of methylene blue （MB） injection, respectively; and Chinese ink （CI）, nanometric activated carbon （NAC） and MB were used as controls. Seventy rats with gastric cancer were randomly divided into 7 groups. The 7 kinds of tracer agents were injected into the peritumoral subserosa at 4 points with microacupuncture needle. The dyeing time, discoloration time, number of dyeing lymph nodes, and hepatorenal function of each group were observed. Results （ 1 ） The established rat model of gastric cancer was consistent with experimental requiremen, and the expression of topo I in cancer tissues was significantly enhanced ; （2） The time from the injection to the 1 st station lymph nodes was 20 min, 4 min and 14 s in CI, NAC and MB groups, respectively; and the time of various kinds of coupling media was 19, 27, 41 and 61 s, respectively. The time of various kinds of tracer agents to the 2nd station lymph nodes was similar with that to the 1 st station lymph nodes ; （ 3 ） The average number of dyeing lymph nodes was 2, 7, 8 in CI, NAC and MB groups, respectively ; the number in various kinds of coupling media groups was 8, 8, 9 and 11 respectively ; （4） The average discoloration time was 〉24 h in CI group, 102 min in MB group, and 2-24 h in the rest groups, respectively; （5） No obvious side effect was observed in all groups. Conclusion By targetedly inhibiting the activity of Topo Ⅰin cancer tissues, adequate dosage of irinotecan coupled with MB may significantly prolong the lymph node dyeing and discoloration time of stomach ca

关 键 词：胃癌 淋巴结 伊立替康 亚甲蓝 示踪剂 

分 类 号：R735.2[医药卫生—肿瘤]