Nrf2抗氧化防御应答在镉致鸡胚神经管发育异常中的作用

发布时间：2018-06-13 20:36

  本文选题：镉 + 鸡胚　； 参考：《东北农业大学》2017年硕士论文

【摘要】：镉是环境中毒性最强的污染物之一,其随着食物链的传递在动物或人体内富集,最终引起多种器官和组织的损伤。研究表明镉能透过胎盘屏障进入胚胎并危害早期神经系统发育,但其毒性机制仍不清楚。本研究以HH-4期鸡胚为试验模型,通过卵黄注射方式进行镉暴露,观察HH-12期鸡胚整体及神经管发育情况,检测鸡胚组织抗氧化功能与Nrf2抗氧化防御应答相关因子,结果显示:镉暴露能够引起早期鸡胚死亡率增加、HH-0至HH-12期发育时间延长、胚胎畸形率显著增加,表明镉导致鸡胚发育迟滞与畸形,具有显著的胚胎发育毒性。镉暴露能够引起早期鸡胚神经管标志因子Shh表达量升高,而Pax3和Pax7表达量降低,随着镉浓度增加鸡胚神经管呈现不程度的闭合不全,表明镉诱发神经管发育异常,这可能是镉早期胚胎神经发育毒性的重要机制之一。镉暴露引起鸡胚组织中MDA和H_2O_2含量增加,SOD、CAT、GSH-Px活性与GSH含量显著降低,T-AOC水平下降,表明镉能够增加自由基与脂质过氧化物含量,降低抗氧化酶活性,扰乱鸡胚抗氧化防御系统,最终引发氧化应激,这可能是其致早期胚胎神经管闭合不全的重要机制之一。低剂量镉暴露能够增强Nrf2表达水平,并介导Ⅱ相解毒酶NQO1、HO-1、CAT、GST、GCLC、GCLM、SOD1-3转录增加,而高剂量镉暴露能够抑制这一效应,表明镉能够通过激发Nrf2介导的抗氧化防御应答来拮抗氧化应激,揭示Nrf2抗氧化防御应答在镉致鸡胚早期神经发育中的具有保护作用。
[Abstract]:Cadmium is one of the most toxic pollutants in the environment. With the transfer of food chain, cadmium is enriched in animal or human body, and eventually causes damage to many organs and tissues. It has been shown that cadmium can enter the embryo through placental barrier and endanger the early development of nervous system, but the mechanism of cadmium toxicity is still unclear. In this study, HH-4 stage chicken embryo was used as experimental model. Cadmium exposure was carried out by yolk injection. The development of whole embryo and nerve tube of HH-12 stage chicken embryo was observed. The antioxidant function of chicken embryo and the related factor of Nrf2 antioxidation defense response were detected. The results showed that cadmium exposure could increase the death rate of early chicken embryos and prolong the development time from HH-0 to HH-12, and the rate of embryo malformation was significantly increased, which indicated that cadmium could cause delayed and abnormal development of chicken embryos and had significant developmental toxicity. Cadmium exposure could increase the expression of neural tube marker factor Shh, but decrease the expression of Pax3 and Pax7 in early chicken embryo. With the increase of cadmium concentration, the neural tube of chicken embryo showed incomplete closure, which indicated that cadmium induced abnormal development of neural tube. This may be one of the important mechanisms of neurotoxicity in cadmium early embryo. The contents of MDA and H2O2 in chicken embryo tissue were increased by cadmium exposure. The activity of GSH-Px and the content of GSH decreased significantly, which indicated that cadmium could increase the content of free radical and lipid peroxide, decrease the activity of antioxidant enzyme, and disrupt the antioxidant defense system of chicken embryo. Oxidative stress may be one of the important mechanisms of neural tube insufficiency in early embryo. Low dose cadmium exposure enhanced the expression of Nrf2 and mediated the increase of transcription of phase 鈪，

本文编号：2015332