【摘要】 目的研究苯并[a]芘(benzo[a]pyrene,B[a]P)单独以及与雌二醇联合染毒对小鼠肺组织雌激素受体-β(estrogen receptor,ER-β)表达的影响,探讨雌激素在B[a]P所致小鼠肺癌中的作用。方法雌性昆明种小鼠125只,随机分为5组,每组25只,正常对照组(橄榄油灌胃和皮下注射)、雌二醇组(900μg/kg雌二醇)、B[a]P组(75μmol/kgB[a]P),B[a]P+高剂量雌二醇组(75μmol/kgB[a]P和900μg/kg雌二醇)和B[a]P+低剂量雌二醇组(75μmol/kgB[a]P和300μg/kg雌二醇),B[a]P灌胃,雌二醇皮下注射,灌胃和注射每周一次,持续8周,之后给予8周的恢复期,共16周。手术切除全肺,采用实时定量PCR(Realtime-PCR)和蛋白质印迹(Westernblotting)技术测定小鼠肺组织中ER-β的表达水平。结果B[a]P组和B[a]P+低剂量雌二醇组ER-β基因和蛋白的表达量明显高于正常对照组,差异有统计学意义(P<0.05)。雌二醇组ER-β基因表达高于正常对照组,差异有统计学意义(P<0.05)。B[a]P+高剂量雌二醇组和雌二醇组中ER-β蛋白表达量明显低于B[a]P组,差异有统计学意义(P<0.05)。结论在本研究剂量范围内,随着雌激素剂量的增加,B[a]P和雌二醇联合作用使ER-βmRNA水平和ER-β蛋白表达下调。ER-β途径在雌激素促进B[a]P致肺癌的剂量-反应关系中的作用有待进一步研究。更多还原

【Abstract】 Objective To study the expression of estrogen receptor beta in the lung tissue of mice treaded with B[a]p alone or combined with estrogen (17 β-estradiol, E2) in female Kunming strain mice and to explore the effect of estrogen in the lung cancer of mice induced by benzo[a]pyrene (B[a]P). Methods One hundred and twenty-five female Kunming mice were randomly divided into 5 groups: normal control group was group 1 ;group 2 was treated with subcutaneous injection of estrogen ( 900 μg/kg); group 3 was given B[a]P(75 μmol/kg) by gavage;the last two groups were given the same dosage of B[a]P (75 μmol/kg)plus two different dosage of estrogen: 900 μg/kg and 300 μg/kg. After 8 weeks,there was a recovery period of 8 weeks. Then, the lung tissue was obtained by surgical resection. The expression of estrogen receptor-β gene and estrogen receptor-β protein of the lung tissue was detected by real-time PCR and Western blotting technology respectively. Results The expression of estrogen receptor-β protein and estrogen receptor-β gene in the B[a]P group and the B[a]P plus low dosage estrogen group was significantly higher than the normal group (P<0.05) . The expression of estrogen receptor-β gene in the estrogen group was significantly higher than the normal group. The expression of estrogen receptor-β protein in the B[a]P plus high dosage estrogen group and the estrogen group was significantly lower than the B[a]P group(P<0.05).Conclusion In the dose range of our study,the expression of estrogen receptor-β protein and estrogen receptor-β gene declined with the increase of estrogen. The mechanism needs further exploration.更多还原