https://scholars.lib.ntu.edu.tw/handle/123456789/194460
標題: | 以微量體液化學發光法定量早產兒血液中活性氧及抗氧化狀態來評估與視網膜病變嚴重度之相關性(1/2) | 作者: | 謝武勳 | 關鍵字: | 早產兒;視網膜病變;自由基;抗氧化狀態;化學發光法(chemiluminescence);prematurity;neonate;reactive oxygen species;reactive nitrogen species;free radical;antioxidant status;retinopathy of prematurity;chemiluminescence | 公開日期: | 2004 | 出版社: | 臺北市:國立臺灣大學醫學院小兒科 | 摘要: | 新生嬰兒的生產過程中,常會合併有氧化自由基的侵襲;因為胎兒在母體的子宮內是處 於相對性的缺氧狀況,血氧分壓為20 到50 毫米汞柱,但出生後立即暴露於相對高氧狀態, 血氧分壓為100 毫米汞柱,肺上皮細胞更直接接觸於氧分壓為140 毫米汞柱的空氣中,因此 新生兒一誕生,需馬上面對氧化侵襲的嚴苛考驗。 近年來的研究認為氧氣、一氧化氮等自由基的過量產生可能會造成新生兒,尤其是早產 兒的各種疾病,包括新生兒慢性肺疾,早產兒視網膜病變,壞死性腸炎,溶血性黃疸等。在 懷孕週數低於28 週的早產兒,視網膜病變發生率甚至可高達80%,其中的百分之二十會有 進行性的變化,嚴重者甚至造成視網膜剝離或失明。針對視網膜病變的致病機轉,近年來的 研究傾向於和早產兒體內的活性氧及抗氧狀態有相關性,但是仍缺乏一致性的結論。無法下 定論的其中原因,也許是新生兒單單早產本身就會出現視網膜病變,另一方面也有可能和研 究方法有關,大部分檢查以測試蛋白質或脂類的氧化產物作為間接證據,僅有少數研究直接 測試glutathione 的氧化還原狀態來評估與視網膜病變之相關性,此外,檢驗項目的特異性 值得商榷。台大醫院醫學研究部近年來發展出新的化學發光測定法,僅需採用微量體液即可 分析血中的活性氧化自由基,而且不易造成早產兒的醫源性貧血。針對住在加護病房的早產 兒,在接受氧氣的治療後,可能引起氧化自由基的上昇,造成進一步早產兒的各種病變,值 得作相關的研究。我們希望採用這種化學發光測定法研究活性氧自由基與早產兒視網膜病變 之嚴重度的相關性。 第一年我們已針對足月兒與早產兒各收集?例及?例,分別抽取臍帶血及出生後第三天例 行篩檢時的微量血液作檢驗,比較兩組間之差異;我們發現出生三天後血中的活性氧自由基 比起臍帶血明顯的上昇,確認出生後新生兒對於新環境中相對高氧濃度的反應。此外針對懷 孕週數未滿30 週或出生體重低於2000 公克的早產兒共?例,經由收集5 c.c.臍帶血及出生後 第1, 7, 14, 21, 28 天分別留取淚液來測定淚液中的自由基;並且由視網膜專家定期追蹤與評 估早產兒視網膜病變的發生率與嚴重度,探討氧化自由基及抗氧化狀態與早產兒視網膜病變 之嚴重度的相關性。 Neonates undergo a dramatic change during the process of childbirth by an increase in oxidative aggression. The fetus exchange a low oxygen intrauterine environment, with PO2 of 20-25 mmHg and a low presence of free radicals, for another with a relative high oxygen extrauterine environment, with PO2 of 100 mmHg. This change results in considerable oxidative stress. Damage due to free radicals, including reactive oxygen species and reactive nitrogen species, is thought to be one of the common mechanisms for several neonatal diseases especially in preterm infants. Chronic lung disease of neonate, retinopathy of prematurity, necrotizing enterocolitis, and hemolytic diseases of neonate are accepted as caused by the excessive production of oxygen or nitrogen free radicals. The oxidative aggression suffered by the neonate is counteracted by the maturation of complex antioxidant defense systems, including both enzymatic systems (superoxide dismutase, catalase, glutathione peroxidase, etc.), and non-enzymatic systems (vitamins E, A, C ). Despite the knowledge that has been advanced in recent years regarding the oxidative stress and antioxidant mechanism, there have remained questions about the maternal-fetal transfer of antioxidant defense mechanism and the free radical and antioxidant status in neonates during perinatal period. Retinopathy of prematurity (ROP) is a disease of the incompletely vascularized immature reteina characterized by retinovitreal neovascularization. It develops in more than 80% of premature survivors born at <28 weeks gestation. Some evidences, by estimating the associations between protein oxidation and lipid peroxidation products and retinopathy of prematurity, indirectly suggest that reactive oxygen species and reactive nitrogen species may play important roles in the pathogenesis of ROP. However, direct evidence that oxidation plays a causative role in ROP is limited. It is not always clear whether the association between oxygen and ROP just reflect a higher disease incidence in the very-low- birth-weight infants who receive more oxygen. Besides, the assay procedures of protein oxidation and lipid peroxidation products may be different and nonspecific, newer and more sensitive tests is warranted. We have developed to use a characteristic emission spectrum analysis of the chemiluminescence (CL-spectrum) with small amount of body fluids for the first time to evaluate the specific reactive oxygen species (ROS) activity including H2O2 and HOCl in the plasma and to adapt a chemiluminescence-high performance liquid chromatography (CL-HPLC) for measurement of PCOOH before and after the dialysis session, in the absence and presence of antioxidant treatment. We hypothesize that the contents of free radicals and the antioxidant defense system are different between the preterm infants with ROP and those without ROP. We propose a two-year research project. In the first year of the project, 20 preterm and 20 term infants will be enrolled. We will detect the oxygen free radicals of cord blood and blood/ urine samples collected 3 days after birth from these neonates. In addition, we will prospectively enroll 20 preterm infants with gestational age less than 30 weeks or birth weight less than 2000 grams. The clinical data including birth weight, sex, gestation age, days on oxygen and/or ventilator will be collected. The ROP check-up will be performed by an ophthalmologist regularly after postnatal age of 4 weeks. We will also detect the oxygen free radicals of the tears samples collected on Days 7, 14, 21, 28 after birth in these preterm infants. In the second year of the project, further cases of preterm infants will be enrolled for study. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/22897 | 其他識別: | 922314B002214 | Rights: | 國立臺灣大學醫學院小兒科 |
顯示於: | 醫學系 |
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922314B002214.pdf | 43.61 kB | Adobe PDF | 檢視/開啟 |
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