皮质酮预处理对乌拉坦诱导小鼠肺癌的影响及其机制研究

Study on effects of corticosterone pretreatment on urethane-induced lung cancer and its mechanism in mice

中文关键词: 皮质酮    乌拉坦    肺腺癌    炎症    受体,糖皮质激素

英文关键词: corticosterone  urethane  adenocarcinoma of lung  inflammation  receptors  glucocorticoid

中文摘要:

      目的 探讨皮质酮(CORT)干预对乌拉坦诱导肺腺癌小鼠模型的影响及其潜在机制。方法 将20只SPF级雄性C57BL/6小鼠随机分为对照组(Ctrl,n=8)和CORT组(Cort,n=12)。Cort组饮用含CORT溶液，对照组饮用1%乙醇溶液。干预8周后，2组均以乌拉坦(1 mg/g)腹腔注射，每周1次，共注射10周。第18周取小鼠肺组织及血清，记录肺结节数，行苏木精-伊红(HE)染色观察小鼠肺组织形态。免疫组织化学染色检测糖皮质激素受体(GR)表达；酶联免疫吸附分析检测肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-1β表达；蛋白质印迹法检测TNF-α、IL-6蛋白表达。结果 与Ctrl组相比，Cort组小鼠体重、饮水量、肺结节数减少，炎症细胞浸润减轻(P<0.05)。Cort组肺组织及肺结节中GR表达升高，血清及肺组织中TNF-α、IL-6水平均降低(P<0.05)。结论 长期低剂量CORT干预可一定程度抑制乌拉坦诱导的肺结节形成，其作用可能与GR上调及炎症反应抑制有关。

英文摘要:

      Objective To investigate the effects of corticosterone(CORT)intervention on a urethane-induced lung adenocarcinoma mouse model and its potential mechanism.Methods Twenty SPF-grade male C57BL/6 mice were randomly divided into control group(Ctrl,n=8)and CORT group(Cort,n=12).The Cort group drank the solution containing CORT,while the control group drank the 1%ethanol solution.After 8 weeks of intervention,both groups received intraperitoneal injections of urethane(1 mg/g)once a week for a total of 10 weeks.At week 18,lung tissue and serum were collected.The number of lung nodules was recorded,and hematoxylin-eosin(HE)staining was performed to observe the morphology of lung tissue.Immunohistochemistry was used to detect the expression of glucocorticoid receptor(GR),enzyme-linked immunosorbent assay was used to measure levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β,and western blot was used to detect the protein expression of TNF-α and IL-6.Results Compared with the Ctrl group,the Cort group exhibited reduced body weight,reduced water intake,fewer lung nodule number,and alleviated inflammatory cell infiltration(P<0.05).GR expression was higher in lung tissue and nodules in the Cort group,while the levels of TNF-α and IL-6 in serum and lung tissue were lower(P<0.05).Conclusion Long-term and low-dose CORT intervention can,to some extent,inhibit the formation of urethane-induced lung nodules.This effect may be associated with the upregulation of GR and the suppression of inflammatory responses.