CAJ | 학술논문

目的：通过建立结肠炎相关的结肠癌小鼠动物模型，观察白三烯 B4受体2（leukotriene B4 receptor 2，BLT2）在结肠炎向结肠癌转变过程中 mRNA 和蛋白表达的变化。方法建立 ICR 小鼠结肠炎相关的结肠癌模型，实验分为正常组和模型组，其中模型组以第1次给诱导剂作为 d0,分别于给药后2、3、5、7、9、13和18周不同时间点处死小鼠，取结肠组织，HE 染色观察结肠组织病理学变化，免疫组化法检测小鼠结肠组织 BLT2蛋白的表达，实时定量 PCR 检测小鼠结肠组织 BLT2 mRNA 的表达。结果组织病理学观察发现随着时间的增长，小鼠结肠由轻度炎症逐渐加重，向异型增生转变，最后转变为结肠癌。免疫组化结果显示 BLT2蛋白在正常结肠组织中表达很少，而在炎性病变部位高表达，炎细胞颜色深染；在异型性增生与癌细胞中表达不明显，但在癌组织的间充质及管腔中表达极高。与正常对照组相比，建模后2、13和18周小鼠结肠组织中 BLT2 mRNA 的表达增强（P<0.05），3、5、7和9周表达明显增强（P<0.01）。结论本实验成功复制了小鼠结肠炎相关的结肠癌模型。BLT2在结肠炎发展的过程中表现出规律性变化。由此推测，BLT2在结肠炎向结肠癌转变过程可能发挥着重要的作用。
목적：통과건립결장염상관적결장암소서동물모형，관찰백삼희 B4수체2（leukotriene B4 receptor 2，BLT2）재결장염향결장암전변과정중 mRNA 화단백표체적변화。방법건립 ICR 소서결장염상관적결장암모형，실험분위정상조화모형조，기중모형조이제1차급유도제작위 d0,분별우급약후2、3、5、7、9、13화18주불동시간점처사소서，취결장조직，HE 염색관찰결장조직병이학변화，면역조화법검측소서결장조직 BLT2단백적표체，실시정량 PCR 검측소서결장조직 BLT2 mRNA 적표체。결과조직병이학관찰발현수착시간적증장，소서결장유경도염증축점가중，향이형증생전변，최후전변위결장암。면역조화결과현시 BLT2단백재정상결장조직중표체흔소，이재염성병변부위고표체，염세포안색심염；재이형성증생여암세포중표체불명현，단재암조직적간충질급관강중표체겁고。여정상대조조상비，건모후2、13화18주소서결장조직중 BLT2 mRNA 적표체증강（P<0.05），3、5、7화9주표체명현증강（P<0.01）。결론본실험성공복제료소서결장염상관적결장암모형。BLT2재결장염발전적과정중표현출규률성변화。유차추측，BLT2재결장염향결장암전변과정가능발휘착중요적작용。
Objective To observe mRNA and protein expression of leukotriene B4(LTB4)receptor 2(BLT2)in mice during the course of development from colitis to colitis-associated cancer. Methods ICR mice were used to establish the animal model of colitis-associated colon cancer and randomly divided into control group and experimental group. We began to administer inducer on d0. Mice were sacrificed at 2,3,5,7,9,13,and 18w,respectively. Histopathological changes in colons were examined. The protein and mRNA expression of BLT2 in colons were measured by immunohistochemical assay and real-time quantitative PCR, respectively. Results Histological study showed that with the extension of time,the lesions of mice colons aggravated,first a mild inflammation,then atypical hyperplasia,and finally to colon cancer. Immunohistochemical staining showed that the expression of BLT2 protein was low in normal colon,but high in inflammatory lesions,especially in inflammatory cells. There was no BLT2 expression in atypical hyperplasia and cancer cells,while BLT2 was highly expressed in the stroma and lumans of cancer tissue. Compared with the control group,mRNA expression of BLT2 in the experimental group was significantly higher at 2,13 and 18w(P<0.05);and very significantly higher at 3,5,7 and 9w (P<0.01). Conclusion The mouse model of colitis-associated colon cancer was developed in this study. The expression of BLT2 changed in the course of colitis development,indicating that BLT2 may play an important role in the transition process from colitis to colon cancer.