摘要
目的:探讨邻苯二甲酸二(2-乙基己)酯(DEHP)对大鼠卵巢组织凋亡基因和癌基因表达水平的影响,为评价DEHP的雌性生殖毒性提供科学依据。方法:用不同剂量DEHP灌胃染毒雌性SD大鼠6周,设对照组(玉米油)、低剂量组(100 mg/kg)、中剂量组(500 mg/kg)、高剂量组(1 500 mg/kg),利用荧光定量PCR技术检测卵巢组织凋亡基因(Bcl-2、Caspase-3、Caspase-8、Caspase-9)和癌基因(c-fos、k-ras)mRNA表达的变化。结果:Bcl-2 mRNA表达水平在DEHP高剂量组显著降低,与对照组比较差异具有统计学意义(P<0.01);Caspase-3、Caspase-8和Caspase-9 mRNA表达水平随DEHP染毒剂量升高呈上升趋势,与对照组比较显著升高,差异均有统计学意义(P<0.05或P<0.01)。c-fos mRNA表达量与对照组间的差异无统计学意义(P>0.05),k-ras mRNA表达量在DEHP中剂量组和高剂量组显著高于对照组(P<0.01)。结论:DEHP可能通过线粒体途径激活Caspase通路诱导卵巢细胞凋亡,进而损害大鼠卵巢功能和生殖内分泌功能。且DEHP可激活原癌基因异常表达,具有一定的潜在致癌风险。
OBJECTIVE： To investigate the reproductive toxicity of di（2-ethylhexyl） phthalate （DEHP）, and to assess the expressions of apoptosis genes and oncogenes after DEHP treatment in female SD rats. METHODS：Female SD rats were treated with different doses of DEHP （corn oil group used as control,DEHP treatment including 100 mg/kg,500 mg/kg,1 500 mg/kg） for 6 weeks. The expression levels of apoptosis genes（Bcl-2,Caspase-3,Caspase-8,Caspase-9） and oncogenes （c-fosand k-ras） mRNA were determined by real-time quantitative PCR.RESULTS：Bcl-2 expression level at DEHP 1 500 mg/kg group was significantly decreased in comparison with control group（P＆lt;0.01）. The expression levels ofCaspase-3,Caspase-8 andCaspase-9 mRNA were significantly increased in rat ovarian tissue after DEHP treatment （P〈0.05 orP〈0.01）. c-fos mRNA expression levels showed no significant difference compared with control. k-ras mRNA expression levels increased significantly in DEHP 500 mg/kg and 1 500 mg/kg treatment groups（P〉0.01）.CONCLUSION：DEHP could activate Caspase apoptosis pathway through the mitochondrial pathway,resulting in apoptosis of ovarian cells,leading to further damage of ovarian function and reproductive endocrine function. DEHP could also activate oncogene expression,therefore DEHP could possess potential carcinogenesis risk.
出处
《癌变．畸变．突变》
CAS
CSCD
2014年第5期374-377,381,共5页
Carcinogenesis,Teratogenesis & Mutagenesis
基金
广东省科技计划项目(2013B021800032)
