大豆异黄酮诱导小鼠先天性尿道下裂模型的建立及发病机制的初步探讨

发布时间：2018-06-06 16:04

本文选题：尿道下裂 + 小鼠　；参考：《山西医科大学》2008年硕士论文

【摘要】： 第一部分大豆异黄酮致小鼠尿道下裂动物模型的建立目的:应用大豆异黄酮孕晚期染毒诱导子代雄鼠尿道下裂的建立,为雌激素致尿道下裂的分子作用机制提供进一步研究的基础。方法:45只孕鼠随机分成5组,在孕12-17d连续6d各组每晨9点分别灌胃生理盐水0.2ml/d(A)、己烯雌酚0.5 mg/(kg.d)(B)、大豆异黄酮100 mg/(kg.d)(C)、300 mg/(kg.d)(D)、900 mg/(kg.d)(E),出生时观察小鼠死亡率,出生后4周观察小鼠有无尿道下裂。结果:A,B,C,D,E各组平均死亡率分别为2.0%,18%,3.8%,5.4%,10%。A,B,C,D,E组子代尿道下裂发生率分别为0%(0/80),28%(11/39),0%(0/76),0%(0/67),19%(10/52)。E组子代尿道下裂发生率与A,C,D组比较有统计学差异(P＜0.05)。E组子代尿道下裂发生率与B组比较无统计学差异。结论:应用昆明种小鼠从孕12d开始给予大豆异黄酮900 mg/(kg.d)灌胃,连续给药6d,成功建立小鼠先天性尿道下裂模型。第二部分先天性尿道下裂小鼠血清睾酮和雌二醇含量的测定目的:测定小鼠血清睾酮和雌二醇的含量,初步探讨大豆异黄酮致雄性仔鼠尿道下裂的发生机制。方法:随机选取空白对照组雄性仔鼠10只(F),从大豆异黄酮低(G)、中剂量组(H)各选取非尿道下裂雄性仔鼠10只,从大豆异黄酮高剂量组选取先天性尿道下裂雄性仔鼠10只(I),分别采血用放射免疫分析法测定睾酮(T)和雌二醇(E2),各组之间进行比较。结果:F,G,H,I,4组体内睾酮含量比较有显著统计学差异性(P＜0.05),而雌二醇含量无明显统计学差异性(P＞0.05)。结论:先天性尿道下裂仔鼠与正常对照组比较,体内睾酮含量比较有显著统计学差异性,而雌二醇含量无明显统计学差异性。第三部分先天性尿道下裂小鼠阴茎皮肤及睾丸组织中AR的测定目的:研究大豆异黄酮对雄性仔鼠尿道下裂的发生并进一步检测仔鼠阴茎皮肤和睾丸组织中雄激素受体(AR)的表达,初步探讨其发病机制。方法:随机选取正常对照组雄性仔鼠(J),造模组非尿道下裂仔鼠(K),先天性尿道下裂仔鼠各10只(L),分别取其阴茎皮肤和睾丸组织用免疫组织化学法测定AR的含量。结果:L组阴茎皮肤组织中AR含量明显低于J组和K组(P＜0.05),J组和L组间阴茎皮肤组织中AR含量无明显差异(P＞0.05);而睾丸组织中AR含量三组总体无明显差异性(P＞0.05)。结论:大豆异黄酮诱导小鼠尿道下裂的发生,可能是由于大豆异黄酮导致小鼠阴茎皮肤组织AR的表达下降,从而导致雄激素和其受体的结合下降所致。
[Abstract]:Part one the establishment of mouse hypospadias model induced by soybean isoflavones Aim: to establish hypospadias induced by soybean isoflavones in male offspring and to provide a basis for further study on the molecular mechanism of estrogen induced hypospadias. Methods Forty five pregnant mice were randomly divided into 5 groups. On 12-17 days of gestation, the rats in each group were administrated with normal saline 0.2 ml / d, diethylstilbestrol 0.5 mg / kg / d, soybean isoflavone 100 mg / kg / d, and isoflavones 300 mg / kg / d, respectively. The mortality of mice was observed at birth, and the hypospadias were observed 4 weeks after birth. Results the average mortality rate of the two groups were 2.0 / 1818 and 3.48 / 10, respectively. The incidence of hypospadias in the offspring of the group A: 0 / 80 was 28 / 28 / 28 / 28, respectively. There was no significant difference in the incidence of hypospadias between group E and group B (P < 0.05). The incidence of hypospadias in group E was not significantly different from that in group B (P < 0.05), and the incidence of hypospadias in group E was not significantly higher than that in group B (P < 0.05). The incidence of hypospadias in group E was significantly higher than that in group B (P < 0.05), and the incidence of hypospadias in group E was not significantly different from that in group B (P < 0.05). The incidence of hypospadias in group E was significantly higher than that in group B (P < 0.05). Conclusion: mice model of congenital hypospadias was successfully established by administration of isoflavone (900 mg / kg 路d) by intragastric administration of isoflavone (900 mg / kg 路d) for 6 days from the 12th day of gestation in Kunming mice. Determination of serum testosterone and estradiol in mice with congenital hypospadias Aim: to determine the levels of serum testosterone and estradiol in mice and to explore the mechanism of hypospadias induced by daidzein. Methods: ten male rats in the blank control group were randomly selected. 10 male rats with non-hypospadias were selected from the soybean isoflavone group and the middle dose group. Ten male rats with congenital hypospadias were selected from the high dose group of soybean isoflavones to determine testosterone (T) and estradiol (E _ 2) by radioimmunoassay (RIA). Results there was significant difference in testosterone content between the 4 groups (P < 0.05), but there was no significant difference in estradiol content (P > 0.05). Conclusion: there is significant difference in testosterone content between congenital hypospadias group and normal control group, but there is no significant difference in estradiol content. Determination of AR in penis skin and testicular tissue of mice with congenital hypospadias Aim: to study the effects of soybean isoflavones on hypospadias in male rats and to investigate the expression of androgen receptor ARA in the skin and testis of male rats. Methods: the male rats of normal control group were randomly selected. The rats of non-hypospadias and congenital hypospadias were randomly selected. The contents of AR were measured by immunohistochemical method in the penile skin and testis of 10 rats with congenital hypospadias and 10 rats with congenital hypospadias. Results there was no significant difference in AR content in penile skin tissue between group J and group K (P < 0.05), but there was no significant difference in AR content in testis between group J and group K (P > 0.05). Conclusion: the occurrence of hypospadias induced by soybean isoflavones may be due to the decrease of AR expression in the penile skin of mice resulting in a decrease in the binding of androgen and its receptor.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R-332;R726.9

【引证文献】