| 摘要: | 化學物質被人類廣泛的利用，帶來了方便的生活，然而無可避免的會釋放到環境 中。這類因子具有模仿、加強、干擾、抵抗生物體內賀爾蒙的活動，當它進入生物體內， 會形成假性賀爾蒙干擾原本的內分泌機制，被通稱為「外因性內分泌干擾化學物質 (environmental endorcine disrupting)」，「壬基苯酚」(nonylphenol, NP)就是其中的一種。 Barker提出，胚胎在子宮內的環境會是其長大成年引發疾病產生的次要原因，因 此提出「健康和疾病發展起源(developmental origins of health and disease)」理論。在母體 不利的環境下，會影響胚胎在子宮內細胞分裂、分化，以致於破壞器官或組織的正常發 展。胚胎的改變是因胚胎的附基因(epigenetic)發生變化，雖沒辦法改變 DNA 序列但能 影響基因的表現。相當多的數據懷疑人類或動物成年時得心血管疾病、第二類型糖尿病 及高血壓等慢性疾病，跟其胚胎在母體子宮的營養及暴露在不利的環境相關。根據研究 母體懷孕暴露在 diethylstibestrol 和 bisphenol-A 會影響胚胎的發展，然而壬基苯酚對胚 胎的影響機轉並不清楚。 根據本人的研究，壬基苯酚會刺激雄性大鼠腎上腺皮質細胞，分泌皮質脂酮和醛固 酮。長期血漿類皮質糖增加，造成 Cushing氏徵候羣，其症狀類似代謝症候症，而且醛 固酮更是高血壓的指標，因此本研究擬探討大鼠在妊娠及授乳期間飲用含壬基苯酚的水 對其子孫成年時代謝的作用機轉。
Phenolic compounds are recognized as endocrine-disrupting chemicals (EDCs), because these chemicals cause reproductive disorders and developmental abnormalities in animals. There have been many reports concerning the adverse effects of EDCs on wildlife, human health and the environment, including defects in reproductive function and immune function or behavior and causing cancer. Nonylphenol (NP) has been documented to appear in aquatic environment and sediment, where the concentration has approached mg/l and mg/kg level, respectively. The theory of adult disease resulting secondary to in utero environmental exposure was proposed by Barker over 20 years ago. The theory proposed by Barker and his colleagues is “developmental origins of health and disease”. Numerous studies have been presented that reinforce this theory that environmental stimuli result in permanent changes in metabolism and disease susceptibility. Many of these changes are secondary to epigenetic changes during fetal development. The definition of epigenetics has been molded into the study of phenotypes resulting from changes in the chromosome without alterations in the DNA sequence. Epigenomic alteration involves DNA methylation and histone modification. These two processes have critical roles in development and human disease. Considerable epidemiologic data on humans and animal models have demonstrated that in utero nutrition and environmental exposure influence adult susceptibility to chronic diseases such as cardiovascular diseases, type 2 diabetes and hypertension. Humans are commonly exposed to EDCs, which have been coupled to the disruption of normal developmental processes. In particular, exposure to EDCs during critical stages of differentiation can interfere with hormonal signaling, thus altering development and resulting in aberrant gene expression. Diethylstibestrol (DES), bisphenol-A (BPA) and nonylphenol are EDCs. The effects of diethylstibestrol (DES) and bisphenol-A (BPA) on the developing fetus have been extensively studied. However the effect of nonylphenol on the developing fetus is not studied. Nonylphenol can directly increase corticosterone and aldosterone production in adrenal cells from male rat in our study. Corticosterone and cortisol are glucocorticoids secreted from rat, and human, respectively. Glucocorticoid excess, epitomized by Cushing’s syndrome in human, leads to insulin resistance/type 2 diabetes, dyslipidemia, and a redistribution of fat to visceral depots associated cardiovascular risk. The phenomena are same as metabolism syndrome. Aldosterone is the index of hypertension. Consequently, the study was focusing on the effect of metabolism of adult rat offsprings exposed in nonylphenol water in utero and neonate. The mechanism of nonylphenol on offsprings from the first generation was studied in the first year, and the second generation was studied in second year. |
