协同刺激分子B7-H4在小鼠食管癌前病变中的表达

目的：研究协同刺激分子B7同系物4（B7-H4）在小鼠食管癌前病变中的表达变化，探讨其在食管鳞状细胞癌发生中的作用。方法：133只C57BL/6小鼠，分为对照组42只和诱癌组91只。诱癌组小鼠采用饮水法给予50 μg/mL 4-硝基喹啉-1-氧化物（4NQO）15周，诱导小鼠食管癌前病变。通过苏木素-伊红（HE）染色法评价食管组织病理变化；免疫组化和Western blot检测B7-H4蛋白在食管组织中的表达，Western blot检测B7-H4蛋白在小鼠血清中的表达。结果：从16~28周，4NQO诱癌组小鼠食管组织出现肉眼可见的增厚、凸起、肿块等病理改变。HE染色结果显示，小鼠食管组织癌前病变级别与诱癌时间呈正相关（r=0.55，P < 0.01）。另外，B7-H4在食管组织的表达水平与食管癌前病变级别呈正相关（r=0.57，P < 0.01）。与对照组相比，第26周和第28周诱癌组小鼠食管组织B7-H4蛋白表达显著升高（P < 0.05或P < 0.01）。与正常小鼠相比，高级别上皮内瘤变小鼠血清B7-H4蛋白浓度显著升高（P < 0.05）。结论：小鼠食管癌前病变进程中，B7-H4蛋白在血清和食管组织中表达上调，B7-H4可能参与了食管癌前病变的进程。

Expression of costimulatory molecule B7-H4 during progression of esophageal precancerous conditions in mice

OBJECTIVE: To investigate the costimulatory molecule B7 homolog 4 (B7-H4) expression during progression of esophageal precancerous lesions in mice and to evaluate its clinical significance in esophageal squamous cell carcinoma formation. METHODS: 133 C57BL/6 mice were assigned to the control group (n=42) or 4NQO model group (n=91). 50 μg/mL 4-Nitroquinoline -1-oxide (4NQO) in drinking water was fed to the 4NQO model mice for 15 weeks. Hematoxylin eosin (HE) staining was used to evaluate changes in pathological stages of esophageal tissues. B7-H4 protein expression in esophageal tissues was detected by immunohistochemical staining and Western blot. B7-H4 protein expression in serum was detected by Western blot. RESULTS: From 16th to 28th week,esophageal showed visible pathological changes,such as incrassation,pimplings and lumps. Furthermore,HE staining showed that there was a significant and positive correlation between the esophageal pathological grade and the induction time of carcinogenesis,(r=0.55,P < 0.01). Additionally,B7-H4 protein expression in esophageal tissue was positively correlated with the pathological grade of precancerous lesions(r=0.57,P < 0.01). At 26 th and 28 th week, B7-H4 protein expression increased significantly compared with the control group(P < 0.05 or P < 0.01). Moreover, B7-H4 protein concentration in sera of mice of high grade intraepithelial neoplasia increased significantly compared with the normal mice,P < 0.05. CONCLUSION: B7-H4 expression in esophageal and sera increased gradually during the progression of esophageal precancerous lesions. Therefore,B7-H4 may be involved in the formation of esophageal precancerous conditions.