视黄醇抑制尿烷诱发小鼠肺癌的研究

Inhibition effect of retinol on the urethane-induced lung cancer

目的 探讨视黄醇抑制尿烷诱发小鼠肺癌的效果及其机制。方法 12 0只小鼠均分为 3组 ,对照组腹腔内一次性注射 1ml生理盐水 ,其余 2组均腹腔内一次性注射尿烷 0 .4mg/ g ,然后治疗组每周 2次口服视黄醇 10 μl/次 (含视黄醇 1万IU) ,造模组口服等量精制植物油。 16周末处死动物 ,取出心、肺、肝、肾和脑 ,作常规病理并采用免疫组织化学法检测维甲酸受体 β(RAR β)、核增殖抗原 (PCNA)、细胞周期蛋白D1(cyclinD1)和细胞周期蛋白E(cyclinE)的表达。 结果 造模组 12只小鼠发现肺癌 ,发癌率为 30 .0 % ,治疗组和对照组均无肿瘤形成 (P值均 <0 .0 1) ;造模组有支气管上皮非典型增生的小鼠数明显高于治疗组和对照组 (P <0 .0 5和0 .0 1) ,治疗组亦高于对照组 (P <0 .0 1)。造模组RAR β蛋白阳性表达率低于治疗组和对照组 (P值分别 <0 .0 1和 0 .0 5 ) ;造模组 12只肺癌小鼠中 ,RAR β表达阳性 2只 ,2 8只无肺癌小鼠中RAR β表达阳性 18只 ,两者差异有显著性 (P <0 .0 1)。造模组cyclinD1表达阳性率和过表达率均高于治疗组 (P <0 .0 5和 0 .0 1) ,亦高于对照组(P值均 <0 .0 1) ,治疗组高于对照组 (P值均 <0 .0 5 )。造模组cyclinE表达和过表达率均高于治疗组 (P值均 <0 .0 5 ) ,亦高于对照组 (P值均 <0 .

Objective To investigate the inhibition effect of retinol on urethane induced lung cancer. Methods 120 mice were randomly allocated into three groups, namely the model group, the therapeutic group and the control group. In the 40 mice of control group, 1 ml normal saline was injected intraperitoneally for each. Urethane(0.4 mg/g) was injected intraperitoneally in the model group and the therapeutic group for each respectively, Thereafter, the mice in the therapeutic group were fed with retinol 10 μl (containing retinol 10 000 iu ) for each twice a week. For each in the model group was fed with refined bean oil 10 μl twice a week. By three groups were maintained on common diet. By the end of 16 weeks, the mice of all three groups were killed, with their hearts, lungs, brains, livers and kidneys harvested for pathological studies with HE stain. The expressions of retinoic acid recepter β (RAR-β), proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E were measured with immunohistochemical stain. Results In the model group, lung cancers were found (30.0%) in 12 mice, but no neoplasm developed in the other two groups. Bronchial epithelial dysplasia was found more commonly in the model group than that in the therapeutic group and the control group(P<0.05 and 0.01, respectively), and also more commonly in the therapeutic group than in the control group(P<0.01). The positive rates of expressions of RAR-β protein in the model group were lower than those in the therapeutic group and the control group (P<0.01 and 0.05 respectively). In the model group, positive expressions of RAR-β protein were found in 2 specimens of 12 lung cancers and 18 specimens in 28 without absence of lung cancers, respectively (P<0.01). The positive rates of expression and overexpression of cyclin D were higher in the model group than in the therapeutic group (P<0.05), also higher than those of the control group (both P<0.01). The positive rates of expression and overexpression of cyclin E in the model group were higher than those in the therapeutic group (P<0.05), also higher than those in the control group (P<0.01). PCNA index in the model group was higher than that in the other two groups (P<0.05 and 0.01, respectively). PCNA index in the therapeutic group was also higher than that in the control group (P<0.05). Conclusion Retinol can inhibite the genesis of urethane-induced lung cancer and precancerous lesions, and it might be caused by up-regulation of the expression RAR β and modulation of the cell cycle. (Shanghai Med J, 2004,27:836-839)