【摘要】：重金屬鎘是導致小鼠胎兒畸形以及胎兒宮內生長受限的環(huán)境污染物之一,但是鎘脅迫致小鼠胎兒宮內生長受限的分子機制尚不明確。具體而言,妊娠期胎盤中營養(yǎng)物質轉運,其中包括葡萄糖運輸在鎘脅迫致胎兒宮內生長受限中的作用不明確。在本學位論文研究中,我們采取方法實時定量PCR、West Blot和亞硫酸氫鹽PCR等方法,通過建立鎘脅迫致小鼠胎兒宮內生長受限的動物模型,探究鎘對胎盤中葡萄糖轉運載體GLUTs(glucose transporter)的毒性作用。結果顯示,與正常對照組相比,鎘處理組小鼠胎盤中GLUT3蛋白含量明顯下降。通過亞硫酸氫鹽PCR對小鼠胎盤DNA甲基化水平檢測發(fā)現(xiàn),GLUT3基因啟動子區(qū)序列過度甲基化。但是,在小鼠胎盤中兩個主要的重復序列LINE-1(long interspersed nucleotide element)和IAP(Intracisternal A particles)基因的甲基化水平沒有明顯變化。此外,在小鼠胎盤中甲基化轉移酶(DNA methyltransferase)DNMT3B和DNMT3L的含量隨著鎘處理濃度的增加呈上升趨勢。然而,甲基化轉移酶DNMT1與DNMT3A的表達量沒有明顯變化。實驗結果說明:(1)在妊娠末期,鎘脅迫顯著引起小鼠胎兒與胎盤重量的下降。(2)通過小鼠胎盤和胎兒組織的鎘含量測定發(fā)現(xiàn),鎘在胎盤中積累而不是在胎兒中積累;鎘脅迫引起的胎兒宮內生長受限是間接作用于胎兒,而不是胎盤。(3)鎘脅迫引起的小鼠胎兒宮內生長受限,與胎盤中葡萄糖轉移載體GLUT3的表達量下調有關,GLUT3表達量下降可能是由于甲基化轉移酶DNMT3B和DNMT3L的過表達引起GLUT3基因啟動子區(qū)序列低甲基化而引起的。
[Abstract]:Cadmium is one of the environmental pollutants leading to fetal malformation and fetal growth restriction in mice, but the molecular mechanism of fetal growth restriction induced by cadmium stress is not clear. Specifically, the transport of nutrients, including glucose, in the placenta during pregnancy is unclear in the role of cadmium stress induced fetal growth restriction. In this dissertation, we used methods such as real-time quantitative PCR,West Blot and hydrogen sulfite PCR to establish an animal model of fetal intrauterine growth restriction induced by cadmium stress in mice. To investigate the toxicity of cadmium to glucose transport vector GLUTs (glucose transporter) in placenta. The results showed that the content of GLUT3 protein in the placenta of cadmium treated mice was significantly lower than that of normal control group. By detecting the DNA methylation level of mouse placenta by PCR, we found that the promoter sequence of GLUT3 gene was hypermethylated. However, there was no significant change in methylation level of LINE-1 (long interspersed nucleotide element) and IAP (Intracisternal A particles) genes in mouse placenta. In addition, the contents of methyltransferase (DNA methyltransferase) DNMT3B and DNMT3L in mouse placenta increased with the increase of cadmium concentration. However, there was no significant change in the expression of methyltransferase DNMT1 and DNMT3A. The results showed that: (1) cadmium stress significantly decreased the weight of mouse fetus and placenta at the end of pregnancy. (2) cadmium accumulated in placenta, not in fetus. The fetal intrauterine growth restriction induced by cadmium stress is indirectly acting on the fetus, not the placenta. (3) the fetal intrauterine growth restriction induced by cadmium stress is related to the down-regulation of the expression of glucose transfer vector GLUT3 in the placenta. The decrease of GLUT3 expression may be due to the hypomethylation of the promoter region of GLUT3 gene caused by the overexpression of methyltransferase DNMT3B and DNMT3L.
【學位授予單位】：山西大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R114

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本文編號：2331428