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大豆異黃酮誘導(dǎo)小鼠先天性尿道下裂模型的建立及發(fā)病機(jī)制的初步探討

發(fā)布時(shí)間:2018-06-06 16:04

  本文選題:尿道下裂 + 小鼠; 參考:《山西醫(yī)科大學(xué)》2008年碩士論文


【摘要】: 第一部分大豆異黃酮致小鼠尿道下裂動(dòng)物模型的建立 目的:應(yīng)用大豆異黃酮孕晚期染毒誘導(dǎo)子代雄鼠尿道下裂的建立,為雌激素致尿道下裂的分子作用機(jī)制提供進(jìn)一步研究的基礎(chǔ)。 方法:45只孕鼠隨機(jī)分成5組,在孕12-17d連續(xù)6d各組每晨9點(diǎn)分別灌胃生理鹽水0.2ml/d(A)、己烯雌酚0.5 mg/(kg.d)(B)、大豆異黃酮100 mg/(kg.d)(C)、300 mg/(kg.d)(D)、900 mg/(kg.d)(E),出生時(shí)觀察小鼠死亡率,出生后4周觀察小鼠有無(wú)尿道下裂。 結(jié)果:A,B,C,D,E各組平均死亡率分別為2.0%,18%,3.8%,5.4%,10%。A,B,C,D,E組子代尿道下裂發(fā)生率分別為0%(0/80),28%(11/39),0%(0/76),0%(0/67),19%(10/52)。E組子代尿道下裂發(fā)生率與A,C,D組比較有統(tǒng)計(jì)學(xué)差異(P<0.05)。E組子代尿道下裂發(fā)生率與B組比較無(wú)統(tǒng)計(jì)學(xué)差異。 結(jié)論:應(yīng)用昆明種小鼠從孕12d開(kāi)始給予大豆異黃酮900 mg/(kg.d)灌胃,連續(xù)給藥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睪酮和雌二醇含量的測(cè)定 目的:測(cè)定小鼠血清睪酮和雌二醇的含量,初步探討大豆異黃酮致雄性仔鼠尿道下裂的發(fā)生機(jī)制。 方法:隨機(jī)選取空白對(duì)照組雄性仔鼠10只(F),從大豆異黃酮低(G)、中劑量組(H)各選取非尿道下裂雄性仔鼠10只,從大豆異黃酮高劑量組選取先天性尿道下裂雄性仔鼠10只(I),分別采血用放射免疫分析法測(cè)定睪酮(T)和雌二醇(E2),各組之間進(jìn)行比較。 結(jié)果:F,G,H,I,4組體內(nèi)睪酮含量比較有顯著統(tǒng)計(jì)學(xué)差異性(P<0.05),而雌二醇含量無(wú)明顯統(tǒng)計(jì)學(xué)差異性(P>0.05)。 結(jié)論:先天性尿道下裂仔鼠與正常對(duì)照組比較,體內(nèi)睪酮含量比較有顯著統(tǒng)計(jì)學(xué)差異性,而雌二醇含量無(wú)明顯統(tǒng)計(jì)學(xué)差異性。 第三部分先天性尿道下裂小鼠陰莖皮膚及睪丸組織中AR的測(cè)定 目的:研究大豆異黃酮對(duì)雄性仔鼠尿道下裂的發(fā)生并進(jìn)一步檢測(cè)仔鼠陰莖皮膚和睪丸組織中雄激素受體(AR)的表達(dá),初步探討其發(fā)病機(jī)制。 方法:隨機(jī)選取正常對(duì)照組雄性仔鼠(J),造模組非尿道下裂仔鼠(K),先天性尿道下裂仔鼠各10只(L),分別取其陰莖皮膚和睪丸組織用免疫組織化學(xué)法測(cè)定AR的含量。 結(jié)果:L組陰莖皮膚組織中AR含量明顯低于J組和K組(P<0.05),J組和L組間陰莖皮膚組織中AR含量無(wú)明顯差異(P>0.05);而睪丸組織中AR含量三組總體無(wú)明顯差異性(P>0.05)。 結(jié)論:大豆異黃酮誘導(dǎo)小鼠尿道下裂的發(fā)生,可能是由于大豆異黃酮導(dǎo)致小鼠陰莖皮膚組織AR的表達(dá)下降,從而導(dǎo)致雄激素和其受體的結(jié)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.
【學(xué)位授予單位】:山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2008
【分類(lèi)號(hào)】:R-332;R726.9

【引證文獻(xiàn)】

相關(guān)期刊論文 前1條

1 袁耀美;張茨;白晨;;不同劑量氟他胺誘導(dǎo)小鼠建立尿道下裂及隱睪模型研究[J];新鄉(xiāng)醫(yī)學(xué)院學(xué)報(bào);2012年04期



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