摘要：目的：目前许多研究均已证明稀土镧会导致小鼠睾丸功能的损伤，但是对其是否涉 及 cAMP-CREB/CREM 通路功能紊乱的分子机制尚不明确。方法：80 只 CD-1（ICR）雄 性小鼠（20±2g）被随机分成 4 组(每组 20 只)，包括对照组（0。1% w/v 生理盐水处理）和 1、2 和 4mg/kgBW LaCl3 实验组，连续 90 天灌胃处理雄性小鼠，探讨 LaCl3 致小鼠睾丸 功能损伤是否涉及 cAMP-CREB/CREM 通路的功能紊乱。结果：实验中检测的指标发生统 计学上的显著改变，如精子浓度、精子活动率明显下降，而畸形率显著增加。在光镜下查 看精子外形的改变，发现了对照精子完整，无畸形，而处理组的精子形态异常如出现双头 或双尾畸形，部分鞭毛断裂，精子头掉落。同时，LaCl3 暴露造成交配率，妊娠率，产仔 数显著的下降。睾丸组织中 cAMP 含量、 cAMP 依赖蛋白激酶 A(PKA)蛋白表达水平均 显著下降，而蛋白磷酸酶(PP)活性显著升高，且呈剂量依赖效应。随着 LaCl3 处理雄性小 鼠剂量的增加，cAMP-CREB/CREM 通路中 CREM、p-CREB、LDH-C、TESK、ACT 的 表达均下调，而 CREB、TORC 的表达上调。结论：稀土镧能够使小鼠睾丸的功能受到损 伤，并且能够使得睾丸细胞中 cAMP-CREB/CREM 通路的功能紊乱，这对于进一步开发预 防和治疗稀土镧对人类的生殖损害药物具有重要的意义。85852

毕业论文关键词：稀土镧，睾丸，功能损伤，cAMP-CREB/CREM 通路

The dysfunction of testis in mice caused by lanthanum deficiency involves the dysfunction of cAMP-CREB/CREM pathway

Abstract:Objective: Many previous studies have shown that rate earth element can cause the damage of mouse testis。 However, the molecular mechanisms of the damage involved in the dysfunction of the cAMP-CREB/CREM pathway are not yet clear。Methods: 80 CD-1 (ICR) male mice (20 + 2g) were randomly pided into 4 groups (n = 20)。The control group (0。1% w/v physiological saline treatment) and the experimental group of 1, 2, and 4 mg/kgBW LaCl3 were used to treat male mice for 90 days, which to investigate whether LaCl3 induced testicular dysfunction in mice is related to the dysfunction of cAMP-CREB/CREM pathway。Results: Our findings suggested that sperms’ concentration and sperms’ motility were significantly decreased, while the rate of deformity was significantly increased by LaCl3。 The changes of sperm morphology were observed under light microscope, finding that sperms of the control are intact, no malformed, while he abnormal sperm morphology in the treatment groups, such as the emergence of double head or double tail deformity, part of the flagellum rupturing, sperm head dropping。 At the same time, LaCl3 exposure caused a significant decrease in mating rate, pregnancy rate and litter size。 The content of cAMP and cAMP dependent protein kinase A (PKA) in testicular tissue were significantly decreased, while protein  phosphatase  (PP) increased , and the effect was dose-dependent。 The expression of CREM, p-CREB, LDH-C, TESK and ACT in the cAMP-CREB/CREM pathway was down-regulated, while the expression of CREB and TORC increased。Conclusion: La of rate earth element can make mouse testis function damage, and can make the cAMP-CREB/CREM pathway dysfunction in testis,   which is of great significance for the further development of the drug prevention of reproductive toxicity on human by exposure to rare earth elements。

Key words: Lanthanum; Mice; Testis; cAMP-CREB/CREM pathway

目录

第一部分：研究背景 5

1 稀土元素的特征及应用 5

2 稀土元素的毒效性效应 5

2。1