重復藥物流產小鼠模型后續(xù)妊娠結局及早期妊娠相關分子機制研究
發(fā)布時間:2018-04-11 14:57
本文選題:藥物重復流產 + RU486 ; 參考:《北京協(xié)和醫(yī)學院》2013年碩士論文
【摘要】:藥物流產是指口服藥物達到終止早孕的方法,由于此程序簡單,創(chuàng)傷性小,實用性較強等優(yōu)點使得越來越多的婦女選擇這種方法終止早期妊娠。近年來,在我國選擇藥物流產的未經產婦女、未婚婦女和女性青少年的比例相對較高,其中多次藥物流產的在人工流產中也占有一定比例,使得藥物流產(尤其是多次藥物流產)后再次妊娠結局成為目前人們普遍關注的問題。因此我們建立了藥物重復流產小鼠模型,對經歷兩次藥物流產后小鼠再次妊娠結局和其早孕時期相關分子機制進行了一些探索。 目的:研究重復藥物流產小鼠后續(xù)妊娠過程中的妊娠率、仔鼠存活率和體重的影響及早期妊娠過程中相關分子機制。 方法:利用BALB/c小鼠腹腔注射2mg/kg RU486建立重復藥物流產小鼠模型,記錄后續(xù)生產仔鼠出生時間和體重,并采用免疫組化和實時定量PCR檢測了早孕期間相關分子表達變化。 結果:在連續(xù)觀察的18個交配周期中,實驗組和對照組累積妊娠率(受孕率)基本一致,藥物流產對總體生育力無影響。但在前10個周期內,實驗組生育力與對照組相比表現出延遲/降低(p0.05)。隨著胎次的增加實驗組胎產仔數明顯下降(p0.05)。在對照組1-3胎次中哺乳成活率具有逐漸增加的趨勢;而在實驗組1-3胎次中具有明顯降低的趨勢(直線回歸,F=1680.33,p0.05)。隨著胎次的增加,在哺乳過程中,實驗組雄性小鼠死亡所占比例明顯增高(51.9%-86.2%)。兩組幼鼠體質量比較,雌性仔鼠在對照組與實驗組間無明顯差異(p0.05);實驗組雄性仔鼠體質量低于對照組,尤其是第2胎和第3胎明顯降低(t’=1.6851和t,=1.9231,均p0.05)。妊娠早期相關基因表達檢測的實時定量PCR結果顯示,妊娠D7.5, SGK1、GR在實驗組的表達均低于對照組,具有明顯的統(tǒng)計學差異(p0.05)。P53在實驗組的表達高于對照組,具有顯著性統(tǒng)計學差異(p0.01)。 結論:兩次藥物流產小鼠的后續(xù)妊娠過程中,生育力延遲/降低,隨著胎次的增加產仔率和哺乳成活率明顯下降,并且雄性仔鼠的死亡率明顯升高。在妊娠D7.5, SGK1、GR表達低于對照組,與早期流產的有關。
[Abstract]:Drug abortion is a method of terminating early pregnancy with oral medicine. Because of the advantages of simple procedure, small trauma and strong practicability, more and more women choose this method to terminate early pregnancy.In recent years, the proportion of unmarried women and female adolescents who choose drug abortion in our country is relatively high, among which many drug abortions also account for a certain proportion in induced abortion.Drug abortion (especially multiple drug abortion) has become a common concern at present.Therefore, we established a mouse model of drug repeated abortion, and explored the related molecular mechanism of the second pregnancy outcome and its early pregnancy in mice after two drug abortions.Aim: to study the effects of repeated drug abortion on the pregnancy rate, the survival rate and body weight of newborn mice and the related molecular mechanisms during early pregnancy.Methods: the mouse model of repeated drug abortion was established by intraperitoneal injection of 2mg/kg RU486 into BALB/c mice. The birth time and body weight of the mice were recorded. The expression of related molecules during early pregnancy was detected by immunohistochemistry and real-time quantitative PCR.Results: in 18 consecutive mating cycles, the cumulative pregnancy rate (pregnancy rate) of the experimental group and the control group were basically the same, and the drug abortion had no effect on the overall fertility.But in the first 10 cycles, the fertility of the experimental group was delayed / decreased by 0.05% compared with the control group.With the increase of the number of births, the litter size of the experimental group decreased significantly (p 0.05).The survival rate of breast-feeding increased gradually in the control group (1-3 births), but decreased significantly in the experimental group (linear regression analysis: F = 1680.3p0.05).With the increase of the number of births, the proportion of male mice dying in the experimental group increased significantly during lactation, 51.9% -86.2%.There was no significant difference in body mass between the control group and the experimental group, and the body weight of the male offspring in the experimental group was lower than that in the control group, especially in the second and third embryos. The body weight of the female offspring was significantly lower than that of the control group, especially the second and third embryos, with a significant decrease of 1.6851 and 1.9231, respectively (p0.05).The results of real-time quantitative PCR showed that the expression of D7.5 and SGK1GR in the experimental group was lower than that in the control group, and the expression of p0.05. p53 in the experimental group was significantly higher than that in the control group (p0.01).Conclusion: during the subsequent pregnancy of mice induced by two times of drug abortion, fertility was delayed / decreased, and the birth rate and the survival rate of lactation decreased with the increase of birth order, and the mortality rate of male mice increased obviously.The expression of gr in gestational D 7.5 was lower than that in control group, which was related to early abortion.
【學位授予單位】:北京協(xié)和醫(yī)學院
【學位級別】:碩士
【學位授予年份】:2013
【分類號】:R-332;R719.31
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