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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。
Objective To investigate the expression of estrogen receptor (ER-β) in lung tissue of mice induced by benzo [a] pyrene (B [a] P) alone and in combination with estradiol To investigate the role of estrogen in B [a] P induced lung cancer in mice. Methods A total of 125 female Kunming mice were randomly divided into 5 groups (25 rats in each group), normal control group (olive oil intragastric and subcutaneous injection), estradiol group (900μg / kg estradiol), B [a] P (75 μmol / kg B [a] P), B [a] P + high dose estradiol (75 μmol / kg B [a] P and 900 μg / kg estradiol) and B [a] P + (75 μmol / kg B [a] P and 300 μg / kg estradiol), B [a] P was given orally and estradiol was injected subcutaneously once a day for 8 weeks after gavage and injection, Period, a total of 16 weeks. The whole lungs were removed surgically. Real-time PCR (Realtime-PCR) and Western blotting were used to detect the expression of ER-β in the lung tissue of mice. Results The expression of ER-β gene and protein in B [a] P group and B [a] P + low-dose estradiol group was significantly higher than that in normal control group, with statistical significance (P <0.05). The expression of ER-β in estradiol group was higher than that in normal control group (P <0.05). The expression of ER-βprotein in B [a] P + high-dose estradiol group and estradiol group was significantly lower than that in B [a] P group, the difference was statistically significant (P <0.05). Conclusions The combination of B [a] P and estradiol decreased ER-βmRNA and ER-βprotein expression in the dose range of this study with estrogen dose increase. The role of ER-β pathway in the dose-response relationship of estrogen-induced B [a] P-induced lung cancer remains to be further studied.