去势小鼠肾虚肺癌模型建立后性激素对肺癌发生的作用机制探讨

发布时间：2018-08-22 20:46

【摘要】：目的:探讨雄性去势小鼠和正常小鼠Lewis肺癌移植瘤生长、性激素及其受体表达的差异,了解性激素对肺癌发生的作用机制。方法 :选用24只8~9周龄C57BL/6雄性小鼠,随机分为去势组和对照组各12只。去势组采用经腹部途径双侧睾丸切除术,对照组进行同一部位双侧睾丸周围脂肪切除的假手术。恢复性饲养2周后,采用腋下皮下接种法建立小鼠Lewis肺癌模型。观察各组小鼠体内肿瘤的生长情况,每5 d测量一次肿瘤大小。接种3周后,称取小鼠体质量并取血清,然后采用脱颈法处死小鼠,分别剖取移植瘤和肺组织并称质量。ELISA法检测去势组和对照组血清中雌二醇(estrodiol,E_2)和睾酮(testosterone,T)水平。免疫组织化学法检测小鼠移植瘤与肺组织中雄激素受体(androgen receptor,AR)和雌激素受体(estrogen receptor,ER)α/β的表达情况。结果 :与对照组比较,去势组小鼠术后体质量减轻(P0.05),移植瘤体积增长较快(P0.05),移植瘤和肺组织质量均明显增加(P值均0.05),肺部转移结节数增多(P0.05),血清中E_2和T水平均成倍降低(P值均0.001)。去势组和对照组的肺组织中,AR、ERα和ERβ均高表达,且去势组的高表达率明显高于对照组(P值均0.05);在移植瘤组织中,去势组和对照组的AR和ERα均低表达,而ERβ高表达,且去势组的ERβ高表达率明显高于对照组(P0.05)。结论 :去势可引起小鼠体内性激素水平紊乱,性激素受体表达异常上调,从而使小鼠体质量减轻,移植瘤生长加速,肺部转移结节数增多。推测性激素及其受体水平失衡可能影响肺癌的发生和发展。
[Abstract]:Objective: to investigate the difference of growth, sex hormone and its receptor expression between male ovariectomized mice and normal mice with Lewis lung cancer transplantation, and to understand the mechanism of sex hormone on lung cancer. Methods: 24 8-week old C57BL/6 mice were randomly divided into castration group (n = 12) and control group (n = 12). The ovariectomized group was treated with bilateral orchiectomy via abdominal approach, and the control group was sham-operated with bilateral peri-testicular fat resection at the same site. Lewis lung cancer model of mice was established by subaxillary subcutaneous inoculation after 2 weeks of restorative feeding. Tumor growth was observed in each group and tumor size was measured every 5 days. After 3 weeks of inoculation, the mice were weighed for body weight and serum. Then the mice were killed by neck removal method. The serum levels of estradiol E _ 2 and testosterone (testosterone T) in the ovariectomized group and the control group were detected by enzyme-linked immunosorbent assay (Elisa). The expression of androgen receptor AR and estrogen receptor ER 伪 / 尾 in transplanted tumor and lung tissue of mice were detected by immunohistochemical method. Results: compared with the control group, In ovariectomized group, the body weight decreased (P0.05), the volume of transplanted tumor increased rapidly (P0.05), the mass of transplanted tumor and lung tissue increased significantly (P < 0.05), the number of pulmonary metastatic nodules increased (P0.05), and the levels of E _ 2 and T in serum decreased exponentially (P = 0.001). The expression rate of ER 伪 and ER 尾 in castration group and control group was significantly higher than that in control group (P < 0.05), AR and ER 伪 in castration group and control group were both low, and ER 尾 expression was higher in castration group than in control group (P < 0.05). The high expression rate of ER 尾 in castration group was significantly higher than that in control group (P 0.05). Conclusion: castration can lead to disorder of sex hormone level and abnormal up-regulation of sex hormone receptor expression in mice, which can reduce the body mass, accelerate the growth of transplanted tumor and increase the number of metastatic nodules in lung. It is speculated that the imbalance of sex hormone and its receptor may affect the occurrence and development of lung cancer.
【作者单位】：郑州大学第一附属医院中西医结合科;郑州大学基础医学院;郑州大学第一附属医院肿瘤科;郑州大学第一附属医院综合ICU;河南省肿瘤医院(郑州大学附属肿瘤医院);
【基金】：国家自然科学基金资助项目(编号:81473497) 河南省科技厅社发攻关项目(编号:132102310106) 河南省教育厅自然科学基金资助项目(编号:12A320077)~~
【分类号】：R-332;R734.2

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