大鼠长期摄入贫铀对睾酮合成及StAR、P450scc基因表达的影响

目的 研究长期摄入贫铀(DU)对雄性大鼠生殖功能改变的机制。方法 大鼠长期摄入贫铀,剂量分别为4和40 mgDU·kg^－1·d^－1。在 F₀代20个月,F₁代15个月时,测定其血中性激素含量,并用反转录多聚酶链式反应(RT-PCR)研究在睾酮(T)合成中起限速作用的类固醇合成急性调节蛋白(StAR)和细胞色素P450胆固醇侧链裂解酶(P450scc)基因表达的影响,同时设健康对照组。结果 食入组血清T的含量均低于健康对照组,最低为51.73 U/L,但黄体生成素(LH)、卵泡刺激素(FSH)含量均高于健康对照组。StAR mRNA的表达,除F₁低剂量组(StAR/β-actin半定量值为1.35)上调外,其余组的表达均较健康对照组(1.035)下调;P450scc mRNA的表达在F₀代低、高剂量组较健康对照组(P450scc/β-actin比值为0.313)下调,P450scc/β-actin降至0.21;在F₁代低、高剂量组较健康对照组上调,P450scc/β-actin升至0.623。结论 长期摄入DU,可通过抑制StAR、P450scc mRNA的表达从而干扰T合成途径来抑制雄性的生殖作用。

Effect of long-term depleted uranium ingestion on testosterone production and the expression of StAR and P450scc mRNAs in rats

Objective To explore the effect of long-term depleted uranium (DU)ingestion on testosterone production in rats, and its involvement mechanism. Methods Male and female rats (F0 and F1 respectively) for 160 days, respectively. The contents of testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH) in serum were detected in 20 months of F0 generations, and 15 months of F1 generations. RT-PCR was used to analyze the levels of StAR mRNA and P450scc mRNA. Results Compared with the normal control group, the testosterone contents in exposed F0 and F1 generations increased, the lowest was 51.73 U/L, but those of LH and FSH decreased. The expression of StAR mRNA in the low-doze group of F1 generation (StAR/β-actin = 1.35) was up-regulated, down-regulated for other groups.compared with the normal control group (P450scc/β-actin = 0. 313), the expression of P450scc mRNA in the low- and high-dose groups of F0 generation were decreased (P450scc/β-actin = 0.21), and those in the low- and high-dose groups of F1generation were increased (P450scc/β-actin = 0.623) (P ≤ 0.01). Conclusion Long-term DU exposure inhibit the male reproduction by intervening the sexual hormone production through down-regulated the expression of StAR mRNA and P450scc roRNA.