糖皮质激素对食管癌模型小鼠白细胞介素-33表达的影响

Effect of glucocorticoid on IL-33 expression in esophageal carcinoma model mice and its related mechanism

目的观察糖皮质激素对食管癌模型小鼠白细胞介素(IL)-33表达的影响。方法将18只BALB/c小鼠随机分为模型组(Model组)、糖皮质激素组(GC组)和对照组(Control组)。Model组小鼠饮用浓度为100 μg/ml的4NQO水溶液16周后,饮用灭菌注射用水到24周;GC组小鼠在Model组小鼠的基础上,腹腔注射地塞米松(400 μg/只)至24周;Control组小鼠饮用丙二醇水溶液16周后,饮用灭菌注射用水到24周。3组小鼠每隔4周进行尾静脉取血,通过酶联免疫吸附试验(ELISA)法检测IL-33的水平;24周后处死所有小鼠并称取完整食管的质量;通过Western blot检测各组小鼠食管组织IL-33、ST2的蛋白表达水平;免疫组织化学观察IL-33的染色。结果Model组(4.75±1.78) g、GC组(2.06±0.02) g和Control组(0.08±0.01) g小鼠食管重量两两较,差异均有统计学意义(均P<0.05);GC组小鼠食管组织IL-33(238.007±36.091)和ST2(456.018±65.013)蛋白表达相对灰度值显著低于Model组小鼠食管组织IL-33(349.095±78.004)和ST2(871.021±60.015)蛋白相对灰度值,差异均具有统计学意义(P<0.05),Control组小鼠食管组织IL-33(123.075±23.027)和ST2(266.071±34.056)蛋白表达相对值显著低于GC组小鼠,两两比较差异均具有统计学意义(P<0.05)。在第24周,Model组、GC组和Control组3组小鼠血清IL-33水平分别为(381.032±45.013) ng/ml、(168.035±26.078) ng/ml和(103.012±34.055) ng/ml,组间比较差异均有统计学意义(P<0.05)。免疫组织化学染色显示Model组小鼠食管黏膜组织上皮细胞的胞质中IL-33染色最多,其次为GC组和Control组小鼠,3组小鼠IL-33阳性细胞数量分别为9.073±1.035、3.068±1.005和1.023±0.087,组间比较差异均具有统计学意义(P<0.05)。结论IL-33与食管癌显著相关,GC能够通过抑制IL-33/ST2信号转导通路而抑制肿瘤的生长。

Objective To investigate the effect of glucocorticoid (GC) on interleukin (IL)-33 expression in esophageal carcinoma model mice. Methods A total of 18 BALB/c mice were randomly divided into three groups such as Model group, GC group and control group. The mice in Model group drank the concentration of 100 μg/ml 4NQO solution for 16 weeks, then drank sterilized water for injection to 24 weeks;The mice in GC group were injected Dexamethasone (400 μg/mouse) into abdominal cavity for 24 weeks on the basis of the mice in Model group;The mice in Control group drank propylene glycol solution for 16 weeks, then drank sterilized water for injection to 24 weeks. All of the mice were taken blood from tail vein every four weeks. Serum levels of IL-33 were detected by enzyme linked immunosorbent assay (ELISA) method. All mice were sacrificed after 24 weeks and then the quality of intact esophagus were weighed and compared. The expression of IL-33 and ST2 protein in esophageal tissues was detected by Western blotting, and the staining of IL-33 was observed by immunohistochemistry method. Results The esophageal weight in Model group, GC group and Control group was (4.75±1.78),(2.06±0.02) and (0.08±0.01) g, respectivetly. The differences was significantly between the each group (P<0.05). The expression of IL-33 and ST2 protein, the serum level of IL-33 in Model group were significantly higher than those in GC group and Control group. The differences were statistically significant (all P<0.05). The expression of IL-33 and ST2 protein, the serum level of IL-33 in GC group were significantly higher than those in Control group. The differences were also statistically significant (all P<0.05). IL-33 staining was the most frequent in the cytoplasm of epithelial cells of esophageal mucosa in Model group A, followed by GC and Control group. Conclusion IL-33 has a significant correlation with esophageal carcinoma and GC can inhibit tumor growth by inhibiting IL-33/ST2 signal transduction pathway.