本文選題：DEHP　切入點(diǎn)：未成熟睪丸　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:探討新生雄性大鼠短期暴露環(huán)境內(nèi)分泌干擾物鄰苯二甲酸二(2-乙己基)酯DEHP對(duì)其雄性生殖系統(tǒng)發(fā)育和功能的影響。通過分析Nrf2和notch信號(hào)通路中關(guān)鍵信號(hào)分子Nrf2和notch1蛋白表達(dá)情況,以及相關(guān)氧化應(yīng)激損傷指標(biāo)檢測(cè),初步探討Nrf2以及notch信號(hào)通路在DEHP致未成熟睪丸發(fā)育損傷的作用。方法:新生雄性大鼠42只分為:對(duì)照組(玉米油)、DEHP 250mg/kg暴露組、DEHP 500mg/kg暴露組。在生后第1到第15天,分別每日經(jīng)口灌胃玉米油和DEHP。PND36時(shí),每組隨機(jī)取6只,經(jīng)10%水合氯醛麻醉下取材。PND90時(shí),行交配實(shí)驗(yàn)后,全部麻醉下取材,附睪組織做精子計(jì)數(shù)和精子畸形率的檢測(cè)。在PND1,PND10,PND20,PND36以及PND90時(shí),測(cè)量各組雄鼠的AGD。PND36取得的睪丸組織行HE染色、氧化應(yīng)激相關(guān)指標(biāo)檢測(cè)以及關(guān)鍵蛋白notch1、Nrf2的表達(dá)。結(jié)果:與對(duì)照組相比,DEHP 250mg/kg暴露組的AGD長度偏低,而睪丸、附睪臟器系數(shù)、精子計(jì)數(shù)、精子畸形率以及以及交配實(shí)驗(yàn)結(jié)果無明顯差異,睪丸組織可見生精上皮排列稍紊亂。DEHP 500mg/kg組的AGD長度、睪丸臟器系數(shù)較正常對(duì)照組偏低;附睪臟器系數(shù)、合籠實(shí)驗(yàn)結(jié)果與正常對(duì)照組比無顯著性差異,但精子畸形率較正常組顯著性增高,并且組織學(xué)上可見睪丸組織形態(tài)有所改變。DEHP 500mg/kg組,睪丸組織內(nèi)ROS水平、SOD酶活性以及MDA較對(duì)照組明顯增多,差異具有統(tǒng)計(jì)學(xué)意義,Nrf2蛋白以及notch1蛋白表達(dá)量降低;DEHP250mg/kg暴露組,其睪丸組織內(nèi)ROS水平、SOD酶活性及MDA較對(duì)照組升高,但無統(tǒng)計(jì)學(xué)意義,Nrf2以及notch1蛋白的表達(dá)較對(duì)照組降低,差異有統(tǒng)計(jì)學(xué)意義。結(jié)論:新生雄性大鼠短期DEHP 500mg/kg暴露可導(dǎo)致其成年后精子質(zhì)量的下降,突出表現(xiàn)在精子畸形率上;而DEHP 250mg/kg短期暴露對(duì)其成年后生殖功能影響不明顯,但組織學(xué)上仍有輕微改變。DEHP的暴露可以引起睪丸組織氧化壓力的增加,MDA水平升高,使Nrf2表達(dá)降低,可能間接影響notch信號(hào)通路,使notch1蛋白表達(dá)降低。
[Abstract]:Objective: to investigate the effects of environmental endocrine disruptor di-2-ethylhexyl phthalate (DEHP) on the development and function of male reproductive system in neonatal male rats. The key signal components in Nrf2 and notch signaling pathway were analyzed. The expression of Nrf2 and notch1 proteins, And the related indexes of oxidative stress injury, To investigate the effects of Nrf2 and notch signaling pathway on immature testicular development injury induced by DEHP. Methods: Forty-two newborn male rats were divided into two groups: control group (exposed to 250 mg / kg DEHP) and DEHP 500 mg / kg exposure group on the 1st to 15th day after birth. When corn oil and DEHP.PND36 were given orally daily, 6 rats in each group were randomly selected. After mating experiment, the samples were obtained under 10% chloral hydrate anaesthesia. Spermatozoa count and sperm abnormality rate were measured in epididymal tissues. During PND1, PND10, PND20, PND36 and PND90, the testicular tissues obtained from AGD.PND36 of each group were stained with HE. Results: compared with the control group, the AGD length of DEHP 250 mg / kg exposure group was lower, while testicular, epididymal organ coefficient, sperm count, testicular, epididymal organ coefficient, spermatozoa count. There was no significant difference in the rate of sperm abnormality and the results of mating test. The testicular tissue showed that the AGD length, testis organ coefficient and epididymal organ coefficient of the spermatogenic epithelium were slightly disordered, and the testicular organ coefficient was lower than that of the normal control group. There was no significant difference between the cage test and the normal control group, but the rate of sperm malformation was significantly higher than that of the normal group, and histologically, the testicular tissue morphology was changed in the group of 500 mg / kg DEHP. The activity of ROS and MDA in testicular tissue were significantly higher than those in the control group. The expression of Nrf2 protein and notch1 protein were significantly decreased in the testis exposed to 250 mg / kg DEHP, and the activity of ROS and MDA in the testis were higher than those in the control group, and the expression of Nrf2 protein and notch1 protein in the testicular tissue was significantly higher than that in the control group. However, the expression of Nrf2 and notch1 protein in neonatal male rats was significantly lower than that in control group. Conclusion: the short-term exposure of DEHP 500mg / kg in neonatal male rats can lead to the decrease of sperm quality in adulthood, especially in the rate of sperm abnormality. However, the short-term exposure of DEHP 250 mg / kg had no obvious effect on the reproductive function after adulthood, but there was still a slight histological change. DEHP could increase the oxidative pressure of testis and increase the level of Nrf2, which may indirectly affect the notch signaling pathway. The expression of notch1 protein was decreased.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R114

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